© 2003 by The Society for Integrative and Comparative Biology
Diverse Lectin Repertoires in Tunicates Mediate Broad Recognition and Effector Innate Immune Responses1
1 Center of Marine Biotechnology, University of Maryland Biotechnology Institute, 701 E. Pratt Street, Baltimore, Maryland 21202
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It is widely recognized that humoral and phagocyte-associated lectins constitute critical components of innate immunity in vertebrates and invertebrates. Their functions include not only self/non-self recognition but also engaging associated effector mechanisms, such as complement-mediated opsonization and killing of potential pathogens. One of the unresolved questions concerns the diversity in recognition capacity of the lectin repertoire, particularly in those organisms lacking adaptive immunity. In this paper, we discuss evidence suggesting that lectin repertoire in invertebrates and protochordates is highly diversified, and includes most of the lectin classes described so far in vertebrate species, as well as associated effector pathways.
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MOLECULAR DIVERSITY IN NON-SELF RECOGNITION CAPACITIES IN INNATE AND ADAPTIVE IMMUNITY: TUNICATES AS MODEL ORGANISMS |
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Of general concern in the comparison of immune functions among animals that may be regarded as more or less primitive, is any perspective gained on how innate and adaptive immune mechanisms may have evolved. While one approach in this field has been to examine the major phylogenetic divisions in a systematic fashion, others have focused on a comparative analysis of organisms that do and don't possess antibodies, the most refined immune recognition/effector tool. It is widely appreciated that modular rearrangement of V-D-J regions of the variable chains in immunoglobulins generates a wide diversity of recognition capacity (Geller, 2002
). Clearly, the modularity of the genetic elements used to create diversity provide relatively high efficiency of function per "unit" genetic material (a good "bang for the buck"). It is hard to argue with the evolutionary success of antibodies (and other elements of the typical adaptive immune response of vertebrates, such as TCRs, B- and T-cells) in protecting the organism against infection, but that very success begs the question, "what about animals which do not have antibodies?" Antibodies are present in modern elasmobranchs and all later vertebrate taxa, whereas agnathans and all invertebrates groups lack bona fide immunoglobulins. Therefore, while the jawed vertebrate taxa are endowed of both innate and adaptive immunity, invertebrates only rely on the former. If an almost unlimited diversity in recognition capabilites, such as that displayed by immunoglobulins of mammals, is the key to protection against infectious disease, which are the equivalent recognition innate immune mechanisms, which have enabled the invertebrate lineages to succeed in this regard during a substantially longer evolutionary time? Furthermore, if Nature has employed a kind of molecular Darwinism to continuously "perfect" immune mechanisms, then the emergence of antibodies (and genetic recombination as a mechanism for generating diversity in recognition) marks the starting point at which it should be advantageous to select against or streamline the prior—and less efficient—immune recognition molecules with functions that overlap those of immunoglobulins. By corollary, in the progress of evolution Nature would have continuously perfected those prior immune molecules up to that point of molecular competition with the emerging immunoglobulins. Thus, within the deuterostome lineage, it is among the invertebrate taxa closest to the jawed vertebrates where these "prior" immune recognition systems should be relatively most efficient and diversified. As species continued to evolve beyond the protochordates and early chordates, the "pressure" on maintaining a high recognition capacity mediated by lectins would have been "relieved" by the emergence of a new class of molecules, antibodies, which assumed the burden of this function, and performed the task in some respects more efficiently, therefore rendering some of the lectins redundant. It may be speculated that higher organisms did not retain copies of all lectins in their genomes due to a selective advantage in deletion of superfluous genetic material. In order to "discover" those lectins with immune functions vital to the organisms expressing them, our approach was to examine species that apparently do not express antibodies as part of the defense repertoire. One such taxon is the Urochordata or tunicates, a highly diverse group of organisms that live in the widest variety of marine environments spread throughout the globe. Implicit in this description is an appreciation of the diversity of immune challenges encountered in those environments. Tunicates are included within the protochordates, having a notochord during the free-swimming larval stage of development, which in the class Ascidiacea, is lost by metamorphosis into a sessile, solitary or colonial adult stage. The presence of the notochord reveals the close affinities of protochordates to the vertebrate lineage(s), but bona fide immunoglobulins are conspicuously absent. Because tunicates represent one of the most advanced taxa that rely on innate immune molecules that predate the emergence of antibodies, they can be considered extant representatives of a key stage in immune evolution, and the model species of choice in which to address these questions of diversity in innate immune recognition (Vasta et al., 2001; Fujita, 2002).
What could possibly substitute to provide sufficiently diverse recognition capacity for potential pathogens in tunicates? Although immunoglobulin gene rearrangements result in a large collection of recognition molecules to meet the large collection of possible epitopes on pathogen surfaces, each molecule thus generated has a relatively narrow range of recognition properties. Alternatively, recognition of surface moieties or patterns that are common to large and diverse groups of potential pathogens, but are absent in the host, represents an effective strategy for immune recognition. Thus, a similar result is obtained in a smaller collection of immune molecules with broad recognition properties. Because of their specificity for carbohydrate structures ubiquitous in viral, prokaryotic and eukaryotic microbes and parasites, lectins have been proposed to take this role. Early reports of animal lectins focused primarily on their possible functions in fertilization and immune responses. In 1899, the first invertebrate lectin was described as secreted from the albumin gland of the snail Helix pomatia, and having agglutination properties for erythrocytes (Camus, 1899). These were later designated "protectins" to suggest that the lectins defend the eggs against microbial or fungal infection, possibly incorporating the popular concept of the day that neutralization is accomplished by immobilizing the microbes in "cages" formed of cross-linked aggregates. Early studies in arthropod species such as the horseshoe crab Limulus polyphemus, the lobster Homarus americanus, the crab Eupagurus prideauxii, and the spider crab Maia squinado identified lectins by the hemagglutination properties of hemolymph, and provided evidence that these hemolymph lectins agglutinate bacteria, have opsonic properties, and can be induced by infectious challenge (reviewed in Vasta et al., 1999). The latter meet important criteria in mounting an immune response. Contemporary animal lectin research has seen a vast expansion on these foundations, to find lectins from invertebrates and vertebrates, including man, in direct participation in innate immune functions as LPS-binding molecules, opsonins, and complement-activating factors.
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ANIMAL LECTINS: CLASSIFICATION AND ROLE IN INNATE AND ADAPTIVE IMMUNITY |
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Most soluble or membrane animal lectins are oligomers of covalently or non-covalently bound peptide subunits (Lis and Sharon, 1986
). Integral membrane lectins are mostly type II transmembrane proteins characterized by the presence of a short transmembrane hydrophobic domain that anchors the protein to the lipid bilayer, and an extracellular carboxyl-terminal portion that carries the carbohydrate recognition domain (CRD). Soluble lectin subunits also usually carry the CRD on the carboxyl-terminal region, whereas remaining portions of the molecule may exhibit domains with variable structure. The presence of conserved residues within the CRD and properties such as divalent cation or a reducing environment for ligand binding, enabled Drickamer (1988) to identify two major groups of animal lectins: the C- and S-types. Since then, as more primary and three-dimensional structures become available, new animal lectin families, such as the P-type (Kornfeld, 1992), I-type (Powell and Varki, 1995), ficolins (Le et al., 1998), and heparin-binding (Kjellen and Lindahl, 1991) have been identified. In addition, pentraxins, such as C-reactive protein and serum amyloid P are now considered as a distinct lectin family (Vasta, 1990; Drickamer and Taylor, 1993; Powell and Varki, 1995).
C-type lectins
The C-type lectin family includes both soluble and integral membrane proteins characterized by Ca2+ requirement and a sequence motif of invariant and highly conserved amino acids that comprises of approximately 15% of the CRD (Drickamer, 1988). Within this family subgroups of CRDs with greater or less similarity can be identified, such as those associated with D-mannose- (Man) or D-galactose- (Gal) binding (Drickamer, 1992). The CRDs are most frequently contained within larger polypeptides comprising mosaic proteins that include multiple domains. These may consist of fibrillar collagen-like structures, structures similar to those in the core protein of proteoglycans, epidermal growth factor-like domains or structures similar to those proteins that bind RNA (Drickamer, 1988), resulting in structural and functional mosaic or chimeric molecules. C-type lectins function as receptors for endogenous or exogenous ligands, including the cell surfaces of putative microbial pathogens (Drickamer and Taylor, 1993). Based on their gene structures and domain organization, C-type lectins have been subclassified into separate groups. These include the endocytic receptors, collectins, proteoglycan core proteins, selectins, and the mannose-macrophage receptor. The collectins (Holmskov et al., 1993) include the mannose-binding lectins (MBLs; Drickamer, 1988) and conglutinin (Friis-Christiansen et al., 1990) from serum, and the pulmonary surfactant (Lu et al., 1992), with critical roles in innate immunity against viruses (Anders et al., 1990) and bacteria (Kawasaki et al., 1989). NK cell and macrophage receptors, and selectins are also directly or indirectly involved in immune function.
Galectins (formerly, S-type lectins)
Galectins require a reducing environment, but not Ca2+ or other divalent cations, for binding activity to their ligands, mostly ß-galactosyl residues. Their location is mostly in the cytoplasmic or nuclear (galectin-3) compartment, and on plasma membrane, associated through carbohydrate-binding sites. These lectins exhibit considerable similarities in the primary structure, and exhibit a typical sequence motif in the CRDs (Drickamer, 1988; Barondes et al., 1994a; Cooper and Barondes, 1999), different from the C-type lectins. Based on the primary structure and polypeptide architecture of the subunits, galectins are classified as "proto," "chimera," or "tandem-repeat" types, as defined by Hirabayashi and Kasai (1993). Galectin subtypes are numbered following the order of their discovery (Barondes et al., 1994b). Based on the variability of the amino acid residues that bind ligand, galectins are classified as "type I" (or "Conserved") and "type II" (or "Variable") CRDs (Ahmed and Vasta, 1994a). Most galectins preferentially bind lactose, N-acetyllactosamine and lacto-N-biose over the terminal monosaccharide (D-galactose). Although the biological roles of galectins are not fully understood, they have been proposed to mediate cell-cell or cell-extracellular matrix interactions in developmental processes (Hirabayashi, 1997 and references therein). The Mac-2 antigen, one of the best characterized galectins and recently included in the galectin-3 group (Barondes et al., 1994b), is present on the surface of murine macrophages (Frigeri and Liu, 1992) and proposed to be involved in cell adhesion, inflammation and metastasis (Rabinovich et al., 2002). Galectin-3 is expressed in normal human peripheral blood monocytes and its level increases dramatically as human monocytes differentiate into macrophages upon culturing in vitro (Truong et al., 1993). The level of galectin-3 in monocytes and macrophages was shown to be down-regulated by stimuli such as lipopolysaccharide (LPS) and interferon-
and galectin-3 was secreted by monocytes when stimulated by calcium ionophore. Galectin-3 activates human monocytes and causes superoxide release in a carbohydrate-dependent manner, inhibitable by lactose (Yamaoka et al., 1995). Murine galectin-1 and galectin-3 bind complement receptor CR3, and have been proposed to participate in its activation (Dong and Hughes, 1997; Avni et al., 1998).
Ficolins
Like C-type lectins, and C1q, ficolins are oligomeric proteins that exhibit collagen-like domains (Le et al., 1998). However, ficolins are characterized by the presence of fibrinogen-like (FBG) domains, closely related to the C-terminal portions of fibrinogen ß and chains, which contain the sugar binding sites. The vertebrate ficolins bind GlcNAc in a calcium independent manner, but also interact with other non-carbohydrate structures. In man, two ficolins have been characterized (L- and H- ficolin), can function as opsonins for microbial pathogens, and associate with MASP to activate complement (Matsushita et al., 2000).
Pentraxins
C-reactive protein (CRP) is a prototypical acute phase reactant that belongs to a family of proteins (pentraxins) with lectin-like properties, which include binding to carbohydrates and related structures, divalent cation dependence, biological functions and overall molecular structure (Baltz et al., 1982; Uhlenbruck et al., 1982; Hind et al., 1985; Kilpatrik and Volanakis, 1985; Tennent and Pepys, 1994). Pentraxins are disc-shaped cyclic pentamers of identical subunits with Mr ranging from 20,000 to 30,000, which are non-covalently bound in most examples (deBeer et al., 1982). In addition to phosphocholine-binding properties, CRP binds and precipitates galactans (Baltz et al., 1982; Uhlenbruck et al., 1982), fungal extracts (Baldo et al., 1977) and carageenan gums (Liu et al., 1982) in a Ca2+-dependent manner. Serum amyloid P binds the pyruvate acetal group of galactose, and has been considered a vertebrate serum lectin that modulates immune responses (Linn et al., 1984). In addition to binding to carbohydrates, CRP shares with collectins, ficolins, and other lectins that mediate innate immune mechanisms, the property of complement activation (Sunyer et al., 1998; Nonaka, 2001).
I-type lectins
I-type lectins (Powell and Varki, 1995) are membrane receptor proteins within the immunoglobulin superfamily, characteristized by V1-C2n domain structure (Crocker et al., 1994). CD22, a cell surface phosphoglycoprotein present on resting mature B cells, has seven extracellular domains with the binding region in the first two domains (Engel et al., 1995) and recognizes sialylated moieties (Powell et al., 1993). I-type lectins would mediate antigen-dependent B cell responses (Leprince et al., 1993), or promote intercellular adhesion by recognizing ligands on activated lymphocytes, monocytes and endothelial cells (Engel et al., 1993), or macrophages (Crocker et al., 1994).
P-type lectins
Man-6-phosphate receptors, now designated as P-lectins are type I transmembrane proteins present in the Golgi and plasma membrane with roles in intracellular targeting of lysosomal enzymes and transmembrane signal transduction. Two P-lectin types have been described that differ in their binding properties for IGF-II (Kornfeld, 1992). The oligomeric structure of P-lectins is still unclear, but the subunits exhibit a signal sequence and extracytoplasmic, transmembrane, and intracytoplasmic domains. The P-type CRD may exhibit a "cluster effect" similar to that described for the C-type lectins.
Heparin-binding lectins
A number of heparin-binding proteins, such as neural cell adhesion molecule, fibronectin, and endothelial cell growth factors (Kjellen and Lindahl, 1991) have been described and, although some may have been identified as members of established families of proteins, others have been grouped as a separate category of lectins (Roberson et al., 1981; Eloumami et al., 1990). These, together with a number of recently described extracellular matrix-binding proteins such as the hyaluronan-binding proteins, calnexin and calreticulin, ganglioside-binding proteins and sulfoglucuronosyl lipid-binding protein would mediate interactions between cells and the intercellular matrix. Tissues from mammalian nervous systems have been studied in detail and appear to be particularly rich in heparin-binding lectins (Eloumami et al., 1990).
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LECTIN REPERTOIRES IN TUNICATE SPECIES: STRUCTURAL AND FUNCTIONAL ASPECTS |
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SYNOPSISMOLECULAR DIVERSITY IN NON-SELF...ANIMAL LECTINS: CLASSIFICATION...LECTIN REPERTOIRES IN TUNICATE...CONCLUSIONSReferences |
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If lectins mediate innate immune mechanisms in tunicates, a considerable diversity of molecular species, both in terms of distinct structural classes and isoforms, and diversity in carbohydrate specificities would be expected. The presence of lectins meeting these criteria would circumstantially support the proposition that these molecules provide immune protection because, as outlined above, these are some of the requirements to provide a sufficiently broad and redundant non-self recognition capacity in lieu of antibody-generated diversity. Naturally, a tissue expression and localization compatible with such internal defense roles, and a functional connection between the lectin as the recognition component and effector molecules that would eliminate the threat, are additional requirements. We and others have addressed the latter points elsewhere (Vasta et al., 1999
; Sekine et al., 2001; Fujita, 2002). Here we present some evidence and discussion in support of the molecular diversity of lectin species to meet the former criterion. To illustrate the diversity of a lectin repertoire present in a representative tunicate species, multiple lectins isolated from Halocynthia pyriformis are shown in Figure 1 (Panels A, B and C). By contrast, the fact that not every tunicate species follows this pattern can be seen from the more limited lectin diversity found so far in Didemnum candidum (Fig. 1, panel D). We have functionally identified six distinct lectins in H. pyriformis, according to the methodology of isolation. For example, HpyL-I was purified either from formaldehyde-fixed horse RBCs or by BSM-sepharose affinity chromatography followed by size exclusion. Acid-treated Sepharose was the matrix used to isolate HpyL-II, -III, and -IV by affinity chromatography, again followed by size exclusion. HpyL-V and -VI were purified by affinity chromatography on L-fuc-agarose to produce a complex band profile, followed by ion exchange to further isolate single proteins, one of them yielding a "ladder" pattern. The second purification step required in these procedures reflects a multiplicity of lectins with similar monosaccharide specificities. That there are differences in the matrices required to detect the presence of lectins reflects the diversity of sugar recognition properties among the lectins in H. pyriformis. The array of lectins present in H. pyriformis is paralleled by a similarly impressive population of Clavelina picta lectins, again with similarities and distinctions in their recognition properties that provide an array of non-self recognition potential with overlap to provide some degree of redundancy, as would be expected for a molecular recognition system on which survival depends (Table 1). Although other lectin specificities can be found in C. picta, as in the case of the galactose-binding galectin we will discuss further below (O'Leary, Ahmed, and Vasta, manuscript in preparation), the multiple lectins obtained from an L-fucose affinity matrix serve to illustrate the point that structurally diverse lectin species can be isolated on a single immobilized monosaccharide. It is noteworthy that although overlapping to a certain extent, the sugar specificity profiles of these lectins are different from each other. This supports the concept of a structural diversity of lectins, even in those of closely related specificity, within a single tunicate species.
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Beyond the description of multiple lectin species, there are in the literature descriptions of bone fide homologues of mammalian lectins. C-type lectins in C. picta are closely related to mannose-binding lectins and selectins (Vasta et al., 1999
). A C-type lectin from Styela plicata exhibits a collectin-like structure (Raftos et al., 2001). The structure of a C-type lectin isolated from the ascidian Polyandrocarpa misakiensis, in complex with galactose, has been resolved (Poget et al., 1999). Lectins of the C-type are of particular interest with regards to innate immunity in tunicates due to their widely accepted role in innate immunity in mammals. Immunolectins are a novel lectin type recently-discovered in Botryllus schlosseri (Pancer et al., 1997), that contains both a C-type lectin domain and an immunoglobulin-like domain. The presence of lectin domains associated to immunoglobulin-like domains resembles the fibrinogen-related proteins from mollusks (FREPS), described as a multigene family of recognition molecules that mediate defense responses against parasitic trematodes (Adema et al., 1997).
Besides C-type lectins, other lectin classes, such as ficolins, pentraxins, and galectins have been described in tunicates. Ficolins have been recently recognized to function similarly to collectins in mammals, and tunicates also express a ficolin homolog (Kenjo et al., 2001). Pentraxins are acute-phase proteins composed of only lectin-domain oligomers, typically pentamers, which are prototypical components of the acute phase response of vertebrates and, like MBL and other collectins, have both opsonic and complement activation properties. A pentraxin-like protein was isolated from the colonial tunicate Didemnum candidum (Vasta et al., 1986a, 1986b). This galactose-binding lectin is also mitogenic (Vasta et al., 1986c). A thorough search for the presence of galectins in C. picta resulted in the identification of multiple members of this family, with subunit sizes of 14.8 kDa, 15.8 kDa, 33.5 kDa and 37.5 kDa (Ahmed and Vasta, 1994b), one of which was further characterized with respect to primary structure and expression patterns (O'Leary et al., manuscript in preparation). Although lacking structural information that would enable their classification in any of the lectin classes described so far, the numerous reports describing the presence of multiple lectins of diverse specificities in tunicates, further support the notion that a very complex lectin repertoire is present in most species. It is important to point out that every lectin species is frequently heterogeneous with regards to net charge, revealing the presence of multiple isoforms originating from either multiple lectin gene copies, allelic variation, or post-translational modifications of the gene products. This microheterogeneity of the lectin repertoire further expands its molecular diversity and, possibly, its recognition capabilities, and may provide a sufficiently broad non-self recognition capacity for an efficient innate immune recognition system based on recognition of carbohydrate moieties.
The functional connection between lectin recognition of non-self and consequent triggering of innate immune response in a tunicate species is best supported in Halocynthia roretzi, one of the most thoroughly characterized ascidians. In this species there is clear evidence for the presence of a conserved pathway of complement activation that may function as does the mannose-binding lectin (MBL) pathway of complement activation in mammals. The human MBL triggers activation of complement component C3 through specific cleavage by the MBL-associated serine proteases (MASPs; two have been described). A glucose-binding C-type lectin has been implicated in C3 activation in H. roretzi, an observation that is supported by amelioration of phagocytic activity upon depletion of the lectin by immunoprecipitation (Sekine et al., 2001). As a model system for lectin-based immunity, H. roretzi includes most of the elements of the pathway laid out in the mammalian MBL system. Not only has the lectin been described, so have the ficolins (Fujita, 2002), MASPs (Ji et al., 1997) and complement (Nonaka and Azumi, 1999). The presence on integrin-like molecules on the surface of hemocytes may further suggest the presence of complement receptors (Miyazawa et al., 2001). In Ciona intestinalis, the presence of complement has recently been reported (Marino et al., 2002). Likewise, evidence has been presented for the complete lectin-triggered complement activation pathway in C. picta. This colonial species also expresses homologs of each key component of the MBL-like pathway, including an MBL/selectin-like lectin that can recognize non-self and self components, MASP-like molecules, and evidence for complement homologs (Vasta et al., 1999). These findings suggest that the lectin-mediated complement activation pathway is a widespread mechanism in innate immunity of tunicates, rather than an isolated occurrence, and supports the idea that some components of the complement system predate the emergence of the adaptive immune system (Hoffman et al., 1999).
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SYNOPSISMOLECULAR DIVERSITY IN NON-SELF...ANIMAL LECTINS: CLASSIFICATION...LECTIN REPERTOIRES IN TUNICATE...CONCLUSIONSReferences |
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In the past few years it has become widely acknowledged that lectin-mediated innate immunity has a critical instructive role on adaptive immunity, and the latter has "borrowed" from innate immunity effector mechanisms such as complement-mediated killing. Thus, the evolutionary emergence of adaptive immunity system builds on a well perfected and very efficient recognition/effector innate immune system, and adds the properties of genetic recombination, narrow specificity, and immunological memory to the properties of lectins typical of innate immunity such as broad recognition of carbohydrate structures shared among multiple pathogens. These additional features improve the efficiency of the immune system of the organism with the capacity of antibodies in dealing with repeated infectious challenge, an advantage not offered by lectins.
Although considered less complex and specific than adaptive immune mechanisms, vertebrate innate immunity uses multiple strategies for immune surveillance: recognition of "microbial nonself," "missing self," and "induced or altered self." Although it is unclear, that these three recognition strategies are already present in invertebrate taxa, there is strong evidence to indicate that tunicates have lectins able recognize non-self, such as potentially pathogenic pro-and eukaryotic microbes. There is also evidence however, that tunicates express lectins able to recognize self, particularly endogenous glycans in the tunic, extracellular matrix or on the cell surface, and therefore, potentially able to recognize "missing self," and "induced or altered self." One of these self-recognizing lectins is the C-type lectin CPL-III from C. picta, which in addition to recognizing environmental bacteria, also binds the sulfated tunic polysaccharide (Quesenberry et al., unpublished). Another example is the galactose-binding lectin from P. misakiensis, that was reported as an extracellular matrix component specifically induced by budding, and that mediates stem cell aggregation (Kawamura et al., 1991). Therefore, it is possible that the highly evolved innate immune system present in vertebrates, is already well developed in protochordate taxa. Although resolution of the puzzle is still a work in progress, and despite that some pieces are not yet in place, the outline of the MBL-pathway of complement activation in tunicates is well-enough established at present time. It becomes necessary, however, to ask the relevance of this pathway with respect to the overall capacity of the lectin repertoire to deal with challenge. After all, that lectins can trigger effector responses if only a small percentage of potential threats can be recognized by this mechanism, is hardly compelling. Although the opsonic activity of lectins, as demonstrated in most invertebrate taxa, makes them functionally relevant even in the absence of additional effector mechanisms such as complement activation, their ability to involve molecular "partners" that would amplify the spectrum of defense responses to the recognized infectious challenge, however, has a greater impact when taken together. In this context, whether C3 in tunicates exhibits a diversification similar to that found in teleost fish (Sunyer et al., 1997) should be a question of great interest when considering the vast diversity of the tunicate lectin repertoire, and the potential for its components to trigger an equally diverse effector complement system.
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ACKNOWLEDGMENTS |
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This research was supported by Grant MCB-00-77928 from the National Science Foundation to G.R.V.
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FOOTNOTES |
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1 From the Symposium Comparative Immunology presented at the Annual Meeting of the Society for Integrative and Comparative Biology, 2–6 January 2002, at Anaheim, California.
2 Present address: Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Argentina
3 To whom all correspondence should be sent; E-mail: vasta{at}umbi.umd.edu
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Adema, C. M., L. A. Hertel, R. D. Miller, and E. S. Loker. 1997. A family of fibrinogen-related proteins that precipitates parasite-derived molecules is produced by an invertebrate after infection. Proc. Natl. Acad. Sci. U.S.A, 94:8691-8696.
Ahmed, H., and G. R. Vasta. 1994a.. Galectins: Conservation of functionally and structurally relevant amino acid residues defines two types of carbohydrate recognition domains. Glycobiology, 4:545-549.
Ahmed, H., and G. R. Vasta. 1994b.. Galectins from vertebrates and invertebrates: A comparative studies on physicochemical and carbohydrate-binding properties. Glycobiology, 4:724.
Anders, W. M., C. A. Hartley, and D. C. Jackson. 1990. Bovine and mouse serum b inhibitors of influenza A viruses are mannose-binding lectins. Proc. Natl. Acad. Sci. U.S.A, 87:4485-4489.
Avni, O., Z. Pur, E. Yefenof, and M. Baniyash. 1998. Complement receptor 3 of macrophages is associated with galectin-1-like protein. J. Immunol, 160:6151-6158.
Baldo, B. A., T. Fletcher, and J. Pepys. 1977. Isolation of a peptido-polysaccharide from the dermatophyte Epidermophyton floccosum and a study of its reaction with human C-reactive protein and a mouse anti-phosphorylcholine myeloma serum. Immunology, 32:831-842.[ISI][Medline]
Baltz, M. L., F. C. de Beer, A. Feinstein, E. A. Munn, C. P. Milstein, T. C. Fletcher, J. F. March, J. Taylor, C. Bruton, J. R. Clamp, A. J. Davies, and M. B. Pepys. 1982. Phylogenetic aspects of C-reactive protein and related proteins. Ann. N. Y. Acad. Sci, 389:49-75.[ISI][Medline]
Barondes, S. H., D. N. W. Cooper, M. A. Gitt, and H. Leffler. 1994a.. Galectins. Structure and function of a large family of animal lectins. J. Biol. Chem, 269:20807-20810.
Barondes, S. H., V. Castronovo, D. N. W. Cooper, R. D. Cummings, K. Drickamer, T. Feizi, M. A. Gitt, J. Hirabayashi, C. Hughes, K. Kasai, H. Leffler, F. Liu, R. Lotan, A. M. Mercurio, M. Monsigny, S. Pillai, F. Poirer, A. Raz, P. W. J. Rigby, J. W. Rini, and J. L. Wang. 1994b.. Galectins: A family of animal ß-galactoside-binding lectins. Cell, 76:597-598.[CrossRef][ISI][Medline]
Camus, M. L. 1899. Recherches experimentales sur une agglutinine produite par la glande de l'albumen chez l' Helix pomatia. C.R. Acad. Sci, 129:233.
Cooper, D. N. W., and S. H. Barondes. 1999. God must love galectins; He made so many of them. Glycobiology, 9:979-984.
Crocker, P. R., S. Mucklow, V. Bouckson, A. McWilliam, A. C. Willis, S. Gordon, G. Milon, S. Kelm, and P. Bradfield. 1994. Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin-like domains. EMBO J, 13:4490-4503.[ISI][Medline]
deBeer, F. C., M. L. Baltz, E. A. Munn, A. Feinstein, J. Taylor, C. Bruton, J. R. Clamp, and M. B. Pepys. 1982. Isolation and characterization of C-reactive protein and serum amyloid P component in the rat. Immunology, 45:55-70.[ISI][Medline]
Dong, S., and R. C. Hughes. 1997. Macrophage surface glycoproteins binding to galectin-3 (Mac-2-antigen). Glycoconjugate J, 14:267-274.[CrossRef][ISI][Medline]
Drickamer, K. 1988. Two distinct classes of carbohydrate-recognition domains in animal lectins. J. Biol. Chem, 263:9557-9560.
Drickamer, K. 1992. Engineering galactose-binding activity into a C-type mannose-binding protein. Nature, 360:183-186.[CrossRef][Medline]
Drickamer, K., and M. E. Taylor. 1993. Biology of animal lectins. Annu. Rev. Cell Biol, 9:236-264.
Eloumami, H., D. Bladier, D. Caruelle, J. Courty, R. Joubert, and M. Caron. 1990. Soluble heparin-binding lectins from human brain: Purification, specificity and relationship to an heparin-binding growth factor. Int. J. Biochem, 22:539-544.[CrossRef][ISI][Medline]
Engel, P., Y. Nojima, D. Rothstein, L. J. Zhou, G. L. Wilson, J. H. Kehrl, and T. F. Tedder. 1993. The same epitope on CD22 of lymphocytes mediates the adhesion of erythrocytes, T and B lymphocytes, neutrophils, and monocytes. J. Immunol, 150:4719-4732.[Abstract]
Engel, P., N. Wagner, A. S. Miller, and T. F. Tedder. 1995. Identification of the ligand-binding domains of CD22, a member of the immunoglobulin superfamily that uniquely binds a sialic acid-dependent ligand. J. Exp. Med, 181:1581-1586.
Frigeri, L. G., and F.-T. Liu. 1992. Surface expression of functional IgE binding protein, an endogenous lectin, on mast cells and macrophages. J. Immunol, 148:861-869.[Abstract]
Friis-Christiansen, P., S. Thiel, S. Svehag, R. Dessau, P. Svendsen, O. Andersen, S. B. Laursen, and J. C. Jensenius. 1990. In vivo and in vitro antibacterial activity of conglutinin, a mammalian plasma lectin. Scan. J. Immunol, 31:453-460.[CrossRef][ISI][Medline]
Fujita, T. 2002. Evolution of the lectin-complement pathway and its role in innate immunity. Nature Rev. Immunol, 2:346-353.[CrossRef][ISI][Medline]
Geller, M. 2002. V(D)J recombination: Rag proteins, repair factors, and regulation. Annu. Rev. Biochem, 71:101-132.[CrossRef][ISI][Medline]
Hind, C. R. K., P. M. Collins, M. L. Baltz, and M. B. Pepys. 1985. Human serum amyloid P component, a circulating lectin with specificity for the cyclic 4,6-pyruvate acetal of galactose. Biochem. J, 225:107-111.[ISI][Medline]
Hirabayashi, J., and K. Kasai. 1993. The family of metazoan metal-independent ß-galactoside-binding lectins: Structure, function and molecular evolution. Glycobiology, 3:297-304.
Hirabayashi, J.(ed.) 1997. Recent topics on galectins. Trends Glycosci. Glycotechnol, 9:1-180.
Hoffman, J. A., F. C. Kafatos, C. A. Janeway, and R. A. Ezekowitz. 1999. Phylogenetic perspectives in innate immunity. Science, 284:1313-1318.
Holmskov, U., P. Holt, K. B. M. Reid, A. C. Willis, B. Teisner, and J. C. Jensenius. 1993. Purification and characterization of bovine mannan-binding protein. Glycobiology, 3:147-153.
Ji, X., K. Azumi, M. Sasaki, and M. Nonaka. 1997. Ancient origin of the complement lectin pathway revealed by molecular cloning of mannan binding protein-associated serine protease from a urochordate, the Japanese ascidian, Halocynthia roretzi. Proc. Natl. Acad. Sci. U.S.A, 94:6340-6345.
Kawamura, K., S. Fujiwara, and Y. M. Sugino. 1991. Budding-specific lectin induced in epithelial cells is an extracellular matrix component for stem cell aggregation in tunicates. Development, 113:995-1005.[Abstract]
Kawasaki, N., T. Kawasaki, and I. Yamashina. 1989. A serum lectin (mannan-binding protein) has complement-dependent bactericidal activity. J. Biochem, 106:483-489.
Kenjo, A., M. Takahashi, M. Matsushita, Y. Endo, M. Nakata, T. Muzuochi, and T. Fujita. 2001. Cloning and characterization of novel ficolins from the solitary ascidian, Halocynthia roretzi. J. Biol. Chem, 276:19959-19965.
Kilpatrik, J. M., and J. E. Volanakis. 1985. Opsonic properties of C-reactive protein. Stimulation by phorbol myristate acetate enables human neutrophils to phagocytize C-reactive protein coated cells. J. Immunol, 134:3364-3370.[Abstract]
Kjellen, L., and U. Lindahl. 1991. Proteoglycans: Structures and interactions. Annu. Rev. Biochem, 60:443-475.[CrossRef][ISI][Medline]
Kornfeld, S. 1992. Structure and function of the mannose 6-phosphate/insulin-like growth factor II receptors. Annu. Rev. Biochem, 61:307-330.[CrossRef][ISI][Medline]
Le, Y., S. H. Lee, O. L. Kon, and J. Lu. 1998. Human L-ficolin: Plasma levels, sugar specificity, and assignment of its lectin activity to the fibrinogen-like (FBG) domain. FEBS Lett, 425:367-370.[CrossRef][ISI][Medline]
Leprince, C., K. E. Draves, R. L. Geahlen, J. A. Ledbetter, and E. A. Clark. 1993. CD22 associates with the human surface IgM-B-cell antigen receptor complex. Proc. Natl. Acad. Sci. U.S.A, 90:3236-3240.
Linn, J. J., M. E. A. Pereira, R. A. DeLellis, and K. P. W. J. McAdam. 1984. Human amyloid P component: A circulating lectin that modulates immunological responses. Scand. J. Immunol, 19:227-236.[CrossRef][ISI][Medline]
Lis, H., and N. Sharon. 1986. Lectins as molecules and as tools. Ann. Rev. Biochem, 55:35-67.[CrossRef][ISI][Medline]
Liu, T.-Y., F. A. Robey, and C.-M. Wang. 1982. Structural studies of C-reactive protein. Ann. N.Y. Acad. Sci, 389:151.[CrossRef][ISI][Medline]
Lu, J., A. C. Willis, and K. B. M. Reid. 1992. Purification, characterization and cDNA cloning of human lung surfactant protein D. Biochem. J, 284:795-802.[Medline]
Marino, R., Y. Kimura, R. De Santis, J. D. Lambris, and M. R. Pinto. 2002. Complement in urochordates: Cloning and characterization of two C3-like genes in the ascidian Ciona intestinalis. Immunogenetics, 53:1055-1064.[CrossRef][ISI][Medline]
Matsushita, M., Y. Endo, and T. Fujita. 2000. Cutting edge: Complement-activating complex of ficolin and mannose-binding lectin-associated serine protease. J. Immunol, 164:2281-2284.
Miyazawa, S., K. Azumi, and M. Nonaka. 2001. Cloning and characterization of integrin alpha subunits from the solitary ascidian, Halocynthia roretzi. J. Immunol, 166:1710-1715.
Nonaka, M. 2001. Evolution of the complement system. Curr. Opin. Immunol, 13:69-73.[CrossRef][ISI][Medline]
Nonaka, M., and K. Azumi. 1999. Opsonic complement system of the solitary ascidian, Halocynthia roretzi. Dev. Comp. Immunol, 23:421-427.[CrossRef][ISI][Medline]
Pancer, Z., B. Diehl-Seifert, B. Rinkevich, and W. E. G. Müller. 1997. A novel tunicate (Botryllus schlosseri) putative C-type lectin features an immunoglobulin domain. DNA Cell Biol, 16:801-806.[ISI][Medline]
Poget, S. F., G. B. Legge, M. R. Proctor, P. J. G. Butler, M. Bycroft, and R. L. Williams. 1999. The structure of a tunicate C-type lectin from Polyadrocarpa misakiensis complexed with D-galactose. J. Mol. Biol, 290:867-879.[CrossRef][ISI][Medline]
Powell, L. D., D. Sgroi, E. R. Sjoberg, I. Stamenkovic, and A. Varki. 1993. Natural ligands of the B cell adhesion molecule CD22ß carry N-linked oligosaccharides with a-2,6-linked sialic acids that are required for recognition. J. Biol. Chem, 268:7019-7027.
Powell, L. D., and A. Varki. 1995. I-type lectins. J. Biol. Chem, 270:14243-14246.
Rabinovich, G. A., L. G. Baum, N. Tinari, R. Paganelli, C. Natoli, F.-T. Liu, and S. Iacobelli. 2002. Galectins and their ligands: Amplifiers, silencers or tuners of the inflammatory response? Trends Immunol, 23:313-320.[CrossRef][ISI][Medline]
Raftos, D., P. Green, D. Mahajan, R. Newton, S. Pearce, R. Peters, J. Robbins, and S. Nair. 2001. Collagenous lectins in tunicates and the proteolytic activation of complement. Adv. Exp. Med. Biol, 484:229-236.[ISI][Medline]
Roberson, M. M., H. Ceri, P. J. Shadle, and S. H. Barondes. 1981. Heparin-inhibitable lectins: Marked similarities in chicken and rat. J. Supramol. Struct. Cell Biochem, 15:395-402.[CrossRef][ISI][Medline]
Sekine, H., A. Kenjo, K. Azumi, G. Ohi, M. Takahashi, R. Kasukawa, N. Ichikawa, M. Nakata, T. Mizuochi, M. Matsushita, Y. Endo, and T. Fujita. 2001. An ancient lectin-dependent complement system in an ascidian: Novel lectin isolated from the plasma of the solitary ascidian, Halocynthia roretzi. J. Immunol, 167:4504-4510.
Sunyer, J. O., L. Tort, and J. D. Lambris. 1997. Diversity of the third form of complement, C3, in fish: Functional characterization of five forms of C3 in the diploid fish Sparus aurata. Biochem. J, 326:877-881.[Medline]
Sunyer, J. O., I. K. Zarkadis, and J. D. Lambris. 1998. Complement diversity: A mechanism for generating immune diversity. Immunol. Today, 19:510-523.
Tennent, G. A., and M. B. Pepys. 1994. Glycobiology of the pentraxins. Biochem. Soc. Trans, 22:74-79.[ISI][Medline]
Truong, M.-J., V. Gruart, J.-P. Kusnierz, J.-P. Papin, S. Loiseau, A. Capron, and M. Capron. 1993. Human neutrophils express immunoglobulin E (IgE)-binding proteins (Mac2/
BP) of the S-type lectin family: Role in IgE-dependent activation. J. Exp. Med, 177:243-248.
Uhlenbruck, G., J. Solter, E. Janssen, and H. Haupt. 1982. Anti-galactan anti-haemocyanin specificity of CRP. Ann. N.Y. Acad. Sci, 389:476-479.[CrossRef]
Vasta, G. R. 1990. Invertebrate lectins, C-reactive and serum amyloid. Structural relationships and evolution. In J. J. Marchalonis and C. L. Reinisch (eds.), Defense molecules, pp. 183–199. Wiley-Liss, New York.
Vasta, G. R., J. Hunt, J. J. Marchalonis, and W. W. Fish. 1986a.. Galactosyl-binding lectins from the tunicate Didemnum candidum. Purification and physiological characterization. J. Biol. Chem, 261:9174-9181.
Vasta, G. R., and J. J. Marchalonis. 1986b.. Galactosyl-binding lectins from the tunicate Didemnum candidum. Carbohydrate specificity and characterization of the combining site. J. Biol. Chem, 261:9182-9186.
Vasta, G. R., J. J. Marchalonis, and J. Decker. 1986c.. Binding and mitogenic properties of a galactosyl-specific lectin from the tunicate Didemnum candidum for murine thymocytes. J. Immunol, 137:3216-3223.[Abstract]
Vasta, G. R., M. S. Quesenberry, H. Ahmed, and N. O'Leary. 1999. C-type lectins and galectins mediate innate and adaptive immune functions: Their roles in the complement activation pathway. Dev. Comp. Immunol, 23:401-420.[CrossRef][ISI][Medline]
Vasta, G. R., M. S. Quesenberry, H. Ahmed, and N. O'Leary. 2001. Lectins from tunicates: Structure-function relationships in innate immunity. Adv. Exp. Med. Biol, 484:275-287.[ISI][Medline]
Yamaoka, A., I. Kuwabara, L. G. Frigeri, and F.-T. Liu. 1995. A human lectin, galectin-3 (BP/Mac-2), stimulates superoxide production by neutrophils. J. Immunol, 154:3479-3487.[Abstract]
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