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Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. May 15, 1997; 99(10): 2452–2461.
PMCID: PMC508086

Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin.

Abstract

Galectin-9, a beta-galactoside binding lectin, has recently been isolated from murine embryonic kidney. In this study, its biological functions and expression in embryonic, newborn, and adult mice tissues were investigated. By Northern blot analyses, it was found widely distributed and its expression was developmentally regulated. In situ hybridization studies revealed an accentuated expression of galectin-9 in liver and thymus of embryonic mice. In postnatal mice, antigalectin-9 immunoreactivity was observed in various tissues, including thymic epithelial cells. The high expression of galectin-9 in the thymus led us to investigate its role in the clonal deletion of thymocytes. Fusion proteins were generated, which retained lactose-binding activity like the endogenous galectin-9. Galectin-9, at 2.5 microM concentration, induced apoptosis in approximately 30% of the thymocytes, as assessed by terminal deoxytransferase-mediated dUTP nick end labeling method. The apoptotic effect was dose dependent and lactose inhibitable. At higher concentrations, it induced homotypic aggregation of the thymocytes. Electron microscopy revealed approximately 60% of the thymocytes undergoing apoptosis in the presence of galectin-9. By immunofluorescence microscopy, some of the thymocytes undergoing apoptosis had plasmalemmal bound galectin-9. Galectin-9 failed to induce apoptosis in hepatocytes. Taken together, these findings indicate that galectin-9, a developmentally regulated lectin, plays a role in thymocyte-epithelial interactions relevant to the biology of the thymus.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Varki A. Biological roles of oligosaccharides: all of the theories are correct. Glycobiology. 1993 Apr;3(2):97–130. [PubMed]
  • 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. 1994 Feb 25;76(4):597–598. [PubMed]
  • Barondes SH, Cooper DN, Gitt MA, Leffler H. Galectins. Structure and function of a large family of animal lectins. J Biol Chem. 1994 Aug 19;269(33):20807–20810. [PubMed]
  • Hirabayashi J, Kasai K. The family of metazoan metal-independent beta-galactoside-binding lectins: structure, function and molecular evolution. Glycobiology. 1993 Aug;3(4):297–304. [PubMed]
  • Pfeifer K, Haasemann M, Gamulin V, Bretting H, Fahrenholz F, Müller WE. S-type lectins occur also in invertebrates: high conservation of the carbohydrate recognition domain in the lectin genes from the marine sponge Geodia cydonium. Glycobiology. 1993 Apr;3(2):179–184. [PubMed]
  • Couraud PO, Casentini-Borocz D, Bringman TS, Griffith J, McGrogan M, Nedwin GE. Molecular cloning, characterization, and expression of a human 14-kDa lectin. J Biol Chem. 1989 Jan 15;264(2):1310–1316. [PubMed]
  • Gitt MA, Massa SM, Leffler H, Barondes SH. Isolation and expression of a gene encoding L-14-II, a new human soluble lactose-binding lectin. J Biol Chem. 1992 May 25;267(15):10601–10606. [PubMed]
  • Robertson MW, Albrandt K, Keller D, Liu FT. Human IgE-binding protein: a soluble lectin exhibiting a highly conserved interspecies sequence and differential recognition of IgE glycoforms. Biochemistry. 1990 Sep 4;29(35):8093–8100. [PubMed]
  • Oda Y, Herrmann J, Gitt MA, Turck CW, Burlingame AL, Barondes SH, Leffler H. Soluble lactose-binding lectin from rat intestine with two different carbohydrate-binding domains in the same peptide chain. J Biol Chem. 1993 Mar 15;268(8):5929–5939. [PubMed]
  • Gitt MA, Wiser MF, Leffler H, Herrmann J, Xia YR, Massa SM, Cooper DN, Lusis AJ, Barondes SH. Sequence and mapping of galectin-5, a beta-galactoside-binding lectin, found in rat erythrocytes. J Biol Chem. 1995 Mar 10;270(10):5032–5038. [PubMed]
  • Madsen P, Rasmussen HH, Flint T, Gromov P, Kruse TA, Honoré B, Vorum H, Celis JE. Cloning, expression, and chromosome mapping of human galectin-7. J Biol Chem. 1995 Mar 17;270(11):5823–5829. [PubMed]
  • Magnaldo T, Bernerd F, Darmon M. Galectin-7, a human 14-kDa S-lectin, specifically expressed in keratinocytes and sensitive to retinoic acid. Dev Biol. 1995 Apr;168(2):259–271. [PubMed]
  • Hadari YR, Paz K, Dekel R, Mestrovic T, Accili D, Zick Y. Galectin-8. A new rat lectin, related to galectin-4. J Biol Chem. 1995 Feb 17;270(7):3447–3453. [PubMed]
  • Leonidas DD, Elbert BL, Zhou Z, Leffler H, Ackerman SJ, Acharya KR. Crystal structure of human Charcot-Leyden crystal protein, an eosinophil lysophospholipase, identifies it as a new member of the carbohydrate-binding family of galectins. Structure. 1995 Dec 15;3(12):1379–1393. [PubMed]
  • Dyer KD, Rosenberg HF. Eosinophil Charcot-Leyden crystal protein binds to beta-galactoside sugars. Life Sci. 1996;58(23):2073–2082. [PubMed]
  • Cooper DN, Massa SM, Barondes SH. Endogenous muscle lectin inhibits myoblast adhesion to laminin. J Cell Biol. 1991 Dec;115(5):1437–1448. [PMC free article] [PubMed]
  • Gu M, Wang W, Song WK, Cooper DN, Kaufman SJ. Selective modulation of the interaction of alpha 7 beta 1 integrin with fibronectin and laminin by L-14 lectin during skeletal muscle differentiation. J Cell Sci. 1994 Jan;107(Pt 1):175–181. [PubMed]
  • Wells V, Mallucci L. Identification of an autocrine negative growth factor: mouse beta-galactoside-binding protein is a cytostatic factor and cell growth regulator. Cell. 1991 Jan 11;64(1):91–97. [PubMed]
  • Clyman RI, Tannenbaum J, Chen YQ, Cooper D, Yurchenco PD, Kramer RH, Waleh NS. Ductus arteriosus smooth muscle cell migration on collagen: dependence on laminin and its receptors. J Cell Sci. 1994 Apr;107(Pt 4):1007–1018. [PubMed]
  • Baum LG, Pang M, Perillo NL, Wu T, Delegeane A, Uittenbogaart CH, Fukuda M, Seilhamer JJ. Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells. J Exp Med. 1995 Mar 1;181(3):877–887. [PMC free article] [PubMed]
  • Perillo NL, Pace KE, Seilhamer JJ, Baum LG. Apoptosis of T cells mediated by galectin-1. Nature. 1995 Dec 14;378(6558):736–739. [PubMed]
  • van den Brûle FA, Buicu C, Baldet M, Sobel ME, Cooper DN, Marschal P, Castronovo V. Galectin-1 modulates human melanoma cell adhesion to laminin. Biochem Biophys Res Commun. 1995 Apr 17;209(2):760–767. [PubMed]
  • Poirier F, Timmons PM, Chan CT, Guénet JL, Rigby PW. Expression of the L14 lectin during mouse embryogenesis suggests multiple roles during pre- and post-implantation development. Development. 1992 May;115(1):143–155. [PubMed]
  • Cherayil BJ, Weiner SJ, Pillai S. The Mac-2 antigen is a galactose-specific lectin that binds IgE. J Exp Med. 1989 Dec 1;170(6):1959–1972. [PMC free article] [PubMed]
  • 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. 1992 Apr 5;267(10):6983–6990. [PubMed]
  • Frigeri LG, Robertson MW, Liu FT. Expression of biologically active recombinant rat IgE-binding protein in Escherichia coli. J Biol Chem. 1990 Dec 5;265(34):20763–20769. [PubMed]
  • Yamaoka A, Kuwabara I, Frigeri LG, Liu FT. A human lectin, galectin-3 (epsilon bp/Mac-2), stimulates superoxide production by neutrophils. J Immunol. 1995 Apr 1;154(7):3479–3487. [PubMed]
  • Dagher SF, Wang JL, Patterson RJ. Identification of galectin-3 as a factor in pre-mRNA splicing. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1213–1217. [PMC free article] [PubMed]
  • Yang RY, Hsu DK, Liu FT. Expression of galectin-3 modulates T-cell growth and apoptosis. Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6737–6742. [PMC free article] [PubMed]
  • Inohara H, Raz A. Functional evidence that cell surface galectin-3 mediates homotypic cell adhesion. Cancer Res. 1995 Aug 1;55(15):3267–3271. [PubMed]
  • 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. 1994 Nov 29;33(47):14109–14114. [PubMed]
  • Mehul B, Bawumia S, Hughes RC. Cross-linking of galectin 3, a galactose-binding protein of mammalian cells, by tissue-type transglutaminase. FEBS Lett. 1995 Feb 27;360(2):160–164. [PubMed]
  • Wada J, Kumar A, Liu Z, Ruoslahti E, Reichardt L, Marvaldi J, Kanwar YS. Cloning of mouse integrin alphaV cDNA and role of the alphaV-related matrix receptors in metanephric development. J Cell Biol. 1996 Mar;132(6):1161–1176. [PMC free article] [PubMed]
  • Engvall E, Perlmann P. Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry. 1971 Sep;8(9):871–874. [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed]
  • Seglen PO. Preparation of isolated rat liver cells. Methods Cell Biol. 1976;13:29–83. [PubMed]
  • Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. [PMC free article] [PubMed]
  • Sgonc R, Boeck G, Dietrich H, Gruber J, Recheis H, Wick G. Simultaneous determination of cell surface antigens and apoptosis. Trends Genet. 1994 Feb;10(2):41–42. [PubMed]
  • Cooper DN, Barondes SH. Evidence for export of a muscle lectin from cytosol to extracellular matrix and for a novel secretory mechanism. J Cell Biol. 1990 May;110(5):1681–1691. [PMC free article] [PubMed]
  • Chinnaiyan AM, Dixit VM. The cell-death machine. Curr Biol. 1996 May 1;6(5):555–562. [PubMed]
  • Shortman K, Vremec D, Egerton M. The kinetics of T cell antigen receptor expression by subgroups of CD4+8+ thymocytes: delineation of CD4+8+3(2+) thymocytes as post-selection intermediates leading to mature T cells. J Exp Med. 1991 Feb 1;173(2):323–332. [PMC free article] [PubMed]
  • Patel DD, Haynes BF. Cell adhesion molecules involved in intrathymic T cell development. Semin Immunol. 1993 Aug;5(4):282–292. [PubMed]
  • Yin XM, Oltvai ZN, Korsmeyer SJ. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature. 1994 May 26;369(6478):321–323. [PubMed]
  • Hanada M, Aimé-Sempé C, Sato T, Reed JC. Structure-function analysis of Bcl-2 protein. Identification of conserved domains important for homodimerization with Bcl-2 and heterodimerization with Bax. J Biol Chem. 1995 May 19;270(20):11962–11969. [PubMed]
  • Hébert E, Monsigny M. Oncogenes and expression of endogenous lectins and glycoconjugates. Biol Cell. 1993;79(2):97–109. [PubMed]
  • Hsu DK, Hammes SR, Kuwabara I, Greene WC, Liu FT. Human T lymphotropic virus-I infection of human T lymphocytes induces expression of the beta-galactoside-binding lectin, galectin-3. Am J Pathol. 1996 May;148(5):1661–1670. [PMC free article] [PubMed]
  • Ong CJ, Chui D, Teh HS, Marth JD. Thymic CD45 tyrosine phosphatase regulates apoptosis and MHC-restricted negative selection. J Immunol. 1994 Apr 15;152(8):3793–3805. [PubMed]

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