Abstract
Recent investigations on the molecular mechanisms by which our immune system recognizes infections and initiates defense against those infections have led to the proposition of two models explaining the way our innate immunity system functions; the self-nonself model and the Danger model. In this review, the roles of galectin-3 in innate immunity against infections—host-pathogen interactions—will be discussed. We will shed light on the potential contribution of a β-galactoside binding mammalian lectin, galectin-3 as a molecule implicated in innate immunity from the angle of both the self-nonself model and the Danger model. Published in 2004.
Similar content being viewed by others
References
Janeway CA, Jr, Approaching the asymptote? Evolution and revolution in immunology, Cold Spring Harb Symp Quant Biol 54, 1-13 (1989).
Medzhitov R, Janeway CA, Jr, Decoding the patterns of self and nonself by the innate immune system, Science 296, 298-300 (2002).
Matzinger P, Tolerance, Danger, and the extended family, Annu Rev Immunol 12, 991-1045 (1994).
Matzinger P, The Danger model: A renewed sense of self, Science 296, 301-5 (2002).
Mushegian A, Medzhitov R, Evolutionary perspective on innate immune recognition, J Cell Biol 155, 705-10 (2001).
Matzinger P, An innate sense of Danger, Semin Immunol 10, 399- 415 (1998).
Matzinger P, Essay 1: The Danger model in its historical context, Scand J Immunol 54, 4-9 (2001).
Matzinger P, Introduction to the series. Danger model of immunity, Scand J Immunol 54, 2-3 (2001).
Barondes SH, Cooper DN, Gitt MA, Leffler H, Galectins. Structure and function of a large family of animal lectins, J Biol Chem 269, 20807-10 (1994).
Barondes SH, Castronovo V, Cooper DN, Cummings RD, Drickamer K, Feizi T, Gitt MA, Hirabayashi J, Hughes C, Kasai K, et al. Galectins: A family of animal beta-galactoside-binding lectins, Cell 76, 597-8 (1994).
Rabinovich GA, Galectins: An evolutionarily conserved family of animal lectins with multifunctional properties; a trip from the gene to clinical therapy, Cell Death Differ 6, 711-21 (1999).
Liu FT, Galectins: A new family of regulators of inflammation, Clin Immunol 97, 79-88 (2000).
Hughes RC, Galectins as modulators of cell adhesion, Biochimie 83, 667-76 (2001).
Lowe JB, Glycosylation, immunity, and autoimmunity, Cell 104, 809-12 (2001).
Perillo NL, Marcus ME, Baum LG, Galectins: Versatile modulators of cell adhesion, cell proliferation, and cell death, J Mol Med 76, 402-12 (1998).
Cooper DN, Barondes SH, God must love galectins; he made so many of them, Glycobiology 9, 979-84 (1999).
Yang RY, Hsu DK, Yu L, Ni J, Liu FT, Cell cycle regulation by galectin-12, a new member of the galectin superfamily, J Biol Chem 30, 30 (2001).
Visegrady B, Than NG, Kilar F, Sumegi B, Than GN, Bohn H, Homology modelling and molecular dynamics studies of human placental tissue protein 13 (galectin-13), Protein Eng 14, 875-80 (2001).
Dunphy JL, Barcham GJ, Bischof RJ, Young AR, Nash A, Meeusen EN, Isolation and characterization of a novel eosinophilspecific galectin released into the lungs in response to allergen challenge, J Biol Chem 277, 14916-24 (2002).
Hirabayashi J, Kasai K, The family of metazoan metalindependent beta-galactoside-binding lectins: Structure, function and molecular evolution, Glycobiology 3, 297-304 (1993).
Cherayil BJ, Chaitovitz S, Wong C, Pillai S, Molecular cloning of a human macrophage lectin specific for galactose, Proc Natl Acad Sci USA 87, 7324-8 (1990).
Cherayil BJ, Weiner SJ, Pillai S, The Mac-2 antigen is a galactose-specific lectin that binds IgE, J Exp Med 170, 1959-72 (1989).
Massa SM, Cooper DN, Leffler H, Barondes SH, L-29, an endogenous lectin, binds to glycoconjugate ligands with positive cooperativity, Biochemistry 32, 260-7 (1993).
Hsu DK, Zuberi RI, Liu FT, Biochemical and biophysical characterization of human recombinant IgE-binding protein, an S-type animal lectin, J Biol Chem 267, 14167-74 (1992).
Ochieng J, Fridman R, Nangia-Makker P, Kleiner DE, Liotta LA, Stetler-Stevenson WG, Raz A, Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and-9, Biochemistry 33, 14109-14 (1994).
Herrmann J, Turck CW, Atchison RE, Huflejt ME, Poulter L, Gitt MA, Burlingame AL, Barondes SH, Leffler H, Primary structure of the soluble lactose binding lectin L-29 from rat and dog and interaction of its non-collagenous proline-, glycine-, tyrosine-rich sequence with bacterial and tissue collagenase, J Biol Chem 268, 26704-11 (1993).
Pelletier I, Sato S, Specific Recognition and Cleavage of Galectin-3 by Leishmania major through Species-specific Polygalactose Epitope, J Biol Chem 277, 17663-70 (2002).
Mazurek N, Conklin J, Byrd JC, Raz A, Bresalier RS, Phosphorylation of the beta-galactoside-binding protein galectin-3 modulates binding to its ligands, J Biol Chem 275, 36311-5 (2000).
Sparrow CP, Leffler H, Barondes SH, Multiple soluble betagalactoside-binding lectins from human lung, J Biol Chem 262, 7383-90 (1987).
Sato S, Hughes RC, Binding specificity of a baby hamster kidney lectin for H type I and II chains, polylactosamine glycans, and appropriately glycosylated forms of laminin and fibronectin, J Biol Chem 267, 6983-90 (1992).
Lee RT, Ichikawa Y, Allen HJ, Lee YC, Binding characteristics of galactoside-binding lectin (galaptin) from human spleen, J Biol Chem 265, 7864-71 (1990).
Ahmed H, Allen HJ, Sharma A, Matta KL, Human splenic galaptin: Carbohydrate-binding specificity and characterization of the combining site, Biochemistry 29, 5315-9 (1990).
Lobsanov YD, Gitt MA, Leffler H, Barondes SH, Rini JM, X-ray crystal structure of the human dimeric S-Lac lectin, L-14-II, in complex with lactose at 2.9-A resolution, J Biol Chem 268, 27034- 8 (1993).
Lobsanov YD, Gitt MA, Leffler H, Barondes S, Rini JM, Crystallization and preliminary X-ray diffraction analysis of the human dimeric S-Lac lectin (L-14-II), J Mol Biol 233, 553-5 (1993).
Seetharaman J, Kanigsberg A, Slaaby R, Leffler H, Barondes SH, Rini JM, X-ray crystal structure of the human galectin-3 carbohydrate recognition domain at 2.1-A resolution, J Biol Chem 273, 13047-52 (1998).
Henrick K, Bawumia S, Barboni EA, Mehul B, Hughes RC, Evidence for subsites in the galectins involved in sugar binding at the nonreducing end of the central galactose of oligosaccharide ligands: Sequence analysis, homology modeling and mutagenesis studies of hamster galectin-3, Glycobiology 8, 45-57 (1998).
Gorski JP, Liu FT, Artigues A, Castagna LF, Osdoby P, New alternatively spliced form of galectin-3, a member of the betagalactoside-binding animal lectin family, contains a predicted transmembrane-spanning domain and a leucine zipper motif, J Biol Chem 277, 18840-8 (2002).
Sato S, Ouellet N, Pelletier I, Simard M, Rancourt A, Bergeron MG, Role of galectin-3 as an adhesion molecule for neutrophil extravasation during streptococcal pneumonia, J Immunol 168, 1813-22 (2002).
Hughes RC, Secretion of the galectin family of mammalian carbohydrate-binding proteins, Biochim Biophys Acta 1473, 172- 85 (1999).
Rubartelli A, Cozzolino F, Talio M, Sitia RA, novel secretory pathway for interleukin-1b, a protein lacking a signal sequence, EMBO J 9, 1503-10 (1990).
Rubartelli A, Sitia R, Interleukin 1b and thioredoxin are secreted through a novel pathway of secretion, Biochem Soc Trans 19, 255- 9 (1991).
Muesch A, Hartmann E, Rohde K, Rubartelli A, Sitia R, Rapoport TA, A novel pathway for secretory proteins?, Trends Biochem Sci 15, 86-8 (1990).
Andrei C, Dazzi C, Lotti L, Torrisi MR, Chimini G, Rubartelli A, The secretory route of the leaderless protein interleukin 1beta involves exocytosis of endolysosome-related vesicles, Mol Biol Cell 10, 1463-75 (1999).
Friesel R, Maciag T, Fibroblast growth factor prototype release and fibroblast growth factor receptor signaling, Thromb Haemost 82, 748-54 (1999).
Mignatti P, Morimoto T, Rifkin DB, Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex, J Cell Physiol 151, 81-93 (1992).
Florkiewicz RZ, Majack RA, Buechler RD, Florkiewicz E, Quantitative export of FGF-2 occurs through an alternative, energydependent, non-ER/Golgi pathway, J Cell Physiol 162, 388-99 (1995).
Sato S, Burdett I, Hughes RC, Secretion of the baby hamster kidney 30-kDa galactose-binding lectin from polarized and nonpolarized cells: A pathway independent of the endoplasmic reticulum-Golgi complex, Exp Cell Res 207, 8-18 (1993).
Sato S, Hughes RC, Regulation of secretion and surface expression of Mac-2, a galactoside-binding protein of macrophages, J Biol Chem 269, 4424-30 (1994).
Sato S, Hughes RC, Control of Mac-2 surface expression on murine macrophage cell lines, Eur J Immunol 24, 216-21 (1994).
Lindstedt R, Apodaca G, Barondes SH, Mostov KE, Leffler H, Apical secretion of a cytosolic protein by Madin-Darby Canine Kidney cells, J Biol Chem 268, 11750-7 (1993).
Liu FT, Hsu DK, Zuberi RI, Kuwabara I, Chi EY, Henderson WR, Expression and function of galectin-3, a beta-galactoside-binding lectin, in human monocytes and macrophages, Am J Pathol 147, 1016-28 (1995).
Rogelj S, Weinberg RA, Fanning P, Klagsbrun M, Basic fibroblast growth factor fused to a signal peptide transforms cells, Nature 331, 173-5 (1988).
Sato S, Galectin as a molecule of Danger signal, which could evoke immune response to infection, Trends Glycosci Glycotechnol 14, 285-301 (2002).
Sano H, Hsu DK, Yu L, Apgar JR, Kuwabara I, Yamanaka T, Hirashima M, Liu FT, Human galectin-3 is a novel chemoattractant for monocytes and macrophages, J Immunol 165, 2156-64 (2000).
Kuwabara I, Liu FT, Galectin-3 promotes adhesion of human neutrophils to laminin, J Immunol 156, 3939-44 (1996).
Gupta SK, Masinick S, Garrett M, Hazlett LD, Pseudomonas aeruginosa lipopolysaccharide binds galectin-3 and other human corneal epithelial proteins, Inf Immun 65, 2747-53 (1997).
Dong S, Hughes RC, Galectin-3 stimulates uptake of extracellular Ca2+ in human Jurkat T-cells, FEBS Lett 395, 165-9 (1996).
Yamaoka A, Kuwabara I, Frigeri LG, Liu FT, A human lectin, galectin-3 (epsilon bp/Mac-2), stimulates superoxide production by neutrophils, J Immunol 154, 3479-87 (1995).
Karlsson A, Follin P, Leffler H, Dahlgren C, Galectin-3 activates the NADPH-oxidase in exudated but not peripheral blood neutrophils, Blood 91, 3430-8 (1998).
Jeng KC, Frigeri LG, Liu FT, An endogenous lectin, galectin-3 (epsilon BP/Mac-2), potentiates IL-1 production by human monocytes, Immunol Lett 42, 113-6 (1994).
Frigeri LG, Zuberi RI, Liu F-T, epsilonBP, a β-galactoside-binding animal lectin, recognizes IgE receptor (FceRI) and activates mast cells, Biochemistry 32, 7644-9 (1993).
Cortegano I, del Pozo V, Cardaba B, de Andres B, Gallardo S, del Amo A, Arrieta I, Jurado A, Palomino P, Liu FT, Lahoz C, Galectin-3 down-regulates IL-5 gene expression on different cell types, J Immunol 161, 385-9 (1998).
Cortegano I, Pozo V, Cardaba B, Arrieta I, Gallardo S, Rojo M, Aceituno E, Takai T, Verbeek S, Palomino P, Liu FT, Lahoz C, Interaction between galectin-3 and FcgammaRII induces down-regulation of IL-5 gene: Implication of the promoter sequence IL-5REIII, Glycobiology 10, 237-42 (2000).
Nangia-Makker P, Honjo Y, Sarvis R, Akahani S, Hogan V, Pienta KJ, Raz A, Galectin-3 induces endothelial cell morphogenesis and angiogenesis, Am J Pathol 156, 899-909 (2000).
Demetriou M, Granovsky M, Quaggin S, Dennis JW, Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation, Nature 409, 733-9 (2001).
Krugluger W, Frigeri LG, Lucas T, Schmer M, Forster O, Liu FT, Boltz-Nitulescu G, Galectin-3 inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven rat bone marrow cell proliferation and GM-CSF-induced gene transcription, Immunobiology 197, 97-109 (1997).
Medzhitov R, Toll-like receptors and innate immunity, Nature Rev Immunol 1, 135-45 (2001).
Hoffmann JA, Kafatos FC, Janeway CA, Ezekowitz RA, Phylogenetic perspectives in innate immunity, Science 284, 1313-8 (1999).
Mandrell RE, Apicella MA, Lindstedt R, Leffler H, Possible interaction between animal lectins and bacterial carbohydrates, Methods Enzimol 236, 231-54 (1994).
Mey A, Leffler H, Hmama Z, Normier G, Revillard JP, The animal lectin galectin-3 interacts with bacterial lipopolysaccharides via two independent sites, J Immunol 156, 1572-7 (1996).
Haziot A, Hijiya N, Gangloff SC, Silver J, Goyert SM, Induction of a novel mechanism of accelerated bacterial clearance by lipopolysaccharide in CD14-deficient and Toll-like receptor 4-deficient mice, J Immunol 166, 1075-8 (2001).
Haziot A, Ferrero E, Kontgen F, Hijiya N, Yamamoto S, Silver J, Stewart CL, Goyert SM, Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice, Immunity 4, 407-14 (1996).
Weis WI, Drickamer K, Structural basis of lectin-carbohydrate recognition, Annu Rev Biochem 65, 441-73 (1996).
Janeway CA, Travers P, Walport M, Capra JD, In: Immunobiology, 4th ed. (Elsevier Science Ltd, 1999), pp 363-415.
Borrego F, Ulbrecht M, Weiss EH, Coligan JE, Brooks AG, Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis, J Exp Med 187, 813-8 (1998).
Lee RT, Lee YC, Affinity enhancement by multivalent lectincarbohydrate interaction, Glycoconj J 17, 543-51 (2000).
Sacchettini JC, Baum LG, Brewer CF, Multivalent proteincarbohydrate interactions. A new paradigm for supermolecular assembly and signal transduction, Biochemistry 40, 3009-15 (2001).
Ho M-K, Springer TA, MAC-2, a novel 32,000 Mr mouse macrophage subpopulation-specific antigen defined by monoclonal antibodies, J Immunol 128, 1221-7 (1982).
Flotte TJ, Springer TA, Thorbecke GJ, Dendritic cell and macrophage staining by monoclonal antibodies in tissue sections and epidermal sheets, Am J Pathol 111, 112-24 (1983).
Frigeri LG, Liu FT, Surface expression of functional IgE binding protein, an endogenous lectin, on mast cells and macrophages, J Immunol 148, 861-7 (1992).
Moody SF, Molecular variation in Leishmania, Acta Tropica 53, 184-204 (1993).
Berman JD, Human leishmaniasis: Clinical, diagnostic, and chemotherapeutic developments in the last 10 years, Clin Infect Dis 24 (1997).
Bergan T, Pathogenetic factors of Pseudomonas aeruginosa, Scand J Infect Dis Suppl 29, 7-12 (1981).
Yi AK, Tuetken R, Redford T, Waldschmidt M, Kirsch J, Krieg AM, CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species, J Immunol 160, 4755-61 (1998).
Wallin RP, Lundqvist A, More SH, von Bonin A, Kiessling R, Ljunggren HG, Heat-shock proteins as activators of the innate immune system, Trends Immunol 23, 130-5 (2002).
Burgess WH, Maciag T, The heparin-binding (fibroblast) growth factor family of proteins, Annu Rev Biochem 58, 575-606 (1989).
Bertini R, Howard OM, Dong HF, Oppenheim JJ, Bizzarri C, Sergi R, Caselli G, Pagliei S, Romines B, Wilshire JA, Mengozzi M, Nakamura H, Yodoi J, Pekkari K, Gurunath R, Holmgren A, Herzenberg LA, Ghezzi P, Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells, J Exp Med 189, 1783-9 (1999).
Kerkhoff C, Klempt M, Sorg C, Novel insights into structure and function of MRP8 (S100A8) and MRP14 (S100A9), Biochim Biophys Acta 1448, 200-11 (1998).
Dinarello CA, Cannon JC, Mier JW, Multiple biological activities of human recombinant interleukin-1, J Clin Invest 77, 1734-9 (1986).
Louahed J, Zhou Y, Maloy WL, Rani PU, Weiss C, Tomer Y, Vink A, Renauld J, Van Snick J, Nicolaides NC, Levitt RC, Haczku A, Interleukin 9 promotes influx and local maturation of eosinophils, Blood 97, 1035-42 (2001).
Bergeron Y, Ouellet N, Deslauriers AM, Simard M, Olivier M, Bergeron MG, Cytokine kinetics and other host factors in response to pneumococcal pulmonary infection in mice, Infect Immun 66, 912-22 (1998).
Fillion I, Ouellet N, Simard M, Bergeron Y, Sato S, Bergeron MG, Role of chemokines and formyl peptides in pneumococcal pneumonia-induced monocyte/macrophage recruitment, J Immunol 166, 7353-61 (2001).
Colnot C, Ripoche MA, Milon G, Montagutelli X, Crocker PR, Poirier F, Maintenance of granulocyte numbers during acute peritonitis is defective in galectin-3-null mutant mice, Immunology 94, 290-6 (1998).
Hsu DK, Yang RY, Pan Z, Yu L, Salomon DR, Fung-Leung WP, Liu FT, Targeted disruption of the galectin-3 gene results in attenuated peritoneal inflammatory responses, AmJ Pathol 156, 1073-83 (2000).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sato, S., Nieminen, J. Seeing strangers or announcing “danger”: Galectin-3 in two models of innate immunity. Glycoconj J 19, 583–591 (2002). https://doi.org/10.1023/B:GLYC.0000014089.17121.cc
Issue Date:
DOI: https://doi.org/10.1023/B:GLYC.0000014089.17121.cc