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. 1992 May 2;117(4):895–902. doi: 10.1083/jcb.117.4.895

The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide

PMCID: PMC2289454  PMID: 1374413

Abstract

The selectins (lectin-EGF-complement binding-cell adhesion molecules [LEC-CAMs]) are a family of mammalian receptors implicated in the initial interactions between leukocytes and vascular endothelia, leading to lymphocyte homing, platelet binding, and neutrophil extravasation. The three known selectins, L-selectin (leukocyte adhesion molecule-1 [LECAM-1]), E-selectin (endothelial-leukocyte adhesion molecule-1 [ELAM-1]), and P-selectin (GMP-140) share structural features that include a calcium-dependent lectin domain. The sialyl Lewis(x) carbohydrate epitope has been reported as a ligand for both E- and P-selectins. Although L-selectin has been demonstrated to bind to carbohydrates, structural features of potential mammalian carbohydrate ligand(s) have not been well defined. Using an ELISA developed with a sialyl Lewis(x)-containing glycolipid and an E- selectin-IgG chimera, we have demonstrated the direct binding of the L- selectin-IgG chimera to sialyl Lewis(x). This recognition was calcium dependent, and could be blocked by Mel-14 antibody but not by other antibodies. Recognition was confirmed by the ability of cells expressing the native L-selectin to adhere to immobilized sialyl Lewis(x). These data suggest that the sialyl Lewis(x) oligosaccharide may form the basis of a recognition domain common to all three selectins.

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Selected References

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  1. Berg E. L., Robinson M. K., Warnock R. A., Butcher E. C. The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor. J Cell Biol. 1991 Jul;114(2):343–349. doi: 10.1083/jcb.114.2.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  4. Blackburn C. C., Swank-Hill P., Schnaar R. L. Gangliosides support neural retina cell adhesion. J Biol Chem. 1986 Feb 25;261(6):2873–2881. [PubMed] [Google Scholar]
  5. Brandley B. K., Ross T. S., Schnaar R. L. Multiple carbohydrate receptors on lymphocytes revealed by adhesion to immobilized polysaccharides. J Cell Biol. 1987 Aug;105(2):991–997. doi: 10.1083/jcb.105.2.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brandley B. K., Swiedler S. J., Robbins P. W. Carbohydrate ligands of the LEC cell adhesion molecules. Cell. 1990 Nov 30;63(5):861–863. doi: 10.1016/0092-8674(90)90487-y. [DOI] [PubMed] [Google Scholar]
  7. Capon D. J., Chamow S. M., Mordenti J., Marsters S. A., Gregory T., Mitsuya H., Byrn R. A., Lucas C., Wurm F. M., Groopman J. E. Designing CD4 immunoadhesins for AIDS therapy. Nature. 1989 Feb 9;337(6207):525–531. doi: 10.1038/337525a0. [DOI] [PubMed] [Google Scholar]
  8. Collins T., Williams A., Johnston G. I., Kim J., Eddy R., Shows T., Gimbrone M. A., Jr, Bevilacqua M. P. Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1. J Biol Chem. 1991 Feb 5;266(4):2466–2473. [PubMed] [Google Scholar]
  9. Gallatin W. M., Weissman I. L., Butcher E. C. A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature. 1983 Jul 7;304(5921):30–34. doi: 10.1038/304030a0. [DOI] [PubMed] [Google Scholar]
  10. Hallmann R., Jutila M. A., Smith C. W., Anderson D. C., Kishimoto T. K., Butcher E. C. The peripheral lymph node homing receptor, LECAM-1, is involved in CD18-independent adhesion of human neutrophils to endothelium. Biochem Biophys Res Commun. 1991 Jan 15;174(1):236–243. doi: 10.1016/0006-291x(91)90511-5. [DOI] [PubMed] [Google Scholar]
  11. Imai Y., Singer M. S., Fennie C., Lasky L. A., Rosen S. D. Identification of a carbohydrate-based endothelial ligand for a lymphocyte homing receptor. J Cell Biol. 1991 Jun;113(5):1213–1221. doi: 10.1083/jcb.113.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Imai Y., True D. D., Singer M. S., Rosen S. D. Direct demonstration of the lectin activity of gp90MEL, a lymphocyte homing receptor. J Cell Biol. 1990 Sep;111(3):1225–1232. doi: 10.1083/jcb.111.3.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johnston G. I., Cook R. G., McEver R. P. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell. 1989 Mar 24;56(6):1033–1044. doi: 10.1016/0092-8674(89)90636-3. [DOI] [PubMed] [Google Scholar]
  14. Kansas G. S., Spertini O., Stoolman L. M., Tedder T. F. Molecular mapping of functional domains of the leukocyte receptor for endothelium, LAM-1. J Cell Biol. 1991 Jul;114(2):351–358. doi: 10.1083/jcb.114.2.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kuijpers T. W., Hakkert B. C., Hoogerwerf M., Leeuwenberg J. F., Roos D. Role of endothelial leukocyte adhesion molecule-1 and platelet-activating factor in neutrophil adherence to IL-1-prestimulated endothelial cells. Endothelial leukocyte adhesion molecule-1-mediated CD18 activation. J Immunol. 1991 Aug 15;147(4):1369–1376. [PubMed] [Google Scholar]
  16. Larsen E., Palabrica T., Sajer S., Gilbert G. E., Wagner D. D., Furie B. C., Furie B. PADGEM-dependent adhesion of platelets to monocytes and neutrophils is mediated by a lineage-specific carbohydrate, LNF III (CD15). Cell. 1990 Nov 2;63(3):467–474. doi: 10.1016/0092-8674(90)90443-i. [DOI] [PubMed] [Google Scholar]
  17. Lasky L. A., Singer M. S., Yednock T. A., Dowbenko D., Fennie C., Rodriguez H., Nguyen T., Stachel S., Rosen S. D. Cloning of a lymphocyte homing receptor reveals a lectin domain. Cell. 1989 Mar 24;56(6):1045–1055. doi: 10.1016/0092-8674(89)90637-5. [DOI] [PubMed] [Google Scholar]
  18. Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
  19. Leffler H., Barondes S. H. Specificity of binding of three soluble rat lung lectins to substituted and unsubstituted mammalian beta-galactosides. J Biol Chem. 1986 Aug 5;261(22):10119–10126. [PubMed] [Google Scholar]
  20. Lo S. K., Lee S., Ramos R. A., Lobb R., Rosa M., Chi-Rosso G., Wright S. D. Endothelial-leukocyte adhesion molecule 1 stimulates the adhesive activity of leukocyte integrin CR3 (CD11b/CD18, Mac-1, alpha m beta 2) on human neutrophils. J Exp Med. 1991 Jun 1;173(6):1493–1500. doi: 10.1084/jem.173.6.1493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lowe J. B., Stoolman L. M., Nair R. P., Larsen R. D., Berhend T. L., Marks R. M. ELAM-1--dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA. Cell. 1990 Nov 2;63(3):475–484. doi: 10.1016/0092-8674(90)90444-j. [DOI] [PubMed] [Google Scholar]
  22. Luscinskas F. W., Brock A. F., Arnaout M. A., Gimbrone M. A., Jr Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18)-dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium. J Immunol. 1989 Apr 1;142(7):2257–2263. [PubMed] [Google Scholar]
  23. Moore K. L., Varki A., McEver R. P. GMP-140 binds to a glycoprotein receptor on human neutrophils: evidence for a lectin-like interaction. J Cell Biol. 1991 Feb;112(3):491–499. doi: 10.1083/jcb.112.3.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nottenburg C., Gallatin W. M., St John T. Lymphocyte HEV adhesion variants differ in the expression of multiple gene sequences. Gene. 1990 Nov 15;95(2):279–284. doi: 10.1016/0378-1119(90)90372-x. [DOI] [PubMed] [Google Scholar]
  25. Ord D. C., Ernst T. J., Zhou L. J., Rambaldi A., Spertini O., Griffin J., Tedder T. F. Structure of the gene encoding the human leukocyte adhesion molecule-1 (TQ1, Leu-8) of lymphocytes and neutrophils. J Biol Chem. 1990 May 15;265(14):7760–7767. [PubMed] [Google Scholar]
  26. Phillips M. L., Nudelman E., Gaeta F. C., Perez M., Singhal A. K., Hakomori S., Paulson J. C. ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science. 1990 Nov 23;250(4984):1130–1132. doi: 10.1126/science.1701274. [DOI] [PubMed] [Google Scholar]
  27. Picker L. J., Kishimoto T. K., Smith C. W., Warnock R. A., Butcher E. C. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991 Feb 28;349(6312):796–799. doi: 10.1038/349796a0. [DOI] [PubMed] [Google Scholar]
  28. Pigott R., Needham L. A., Edwards R. M., Walker C., Power C. Structural and functional studies of the endothelial activation antigen endothelial leucocyte adhesion molecule-1 using a panel of monoclonal antibodies. J Immunol. 1991 Jul 1;147(1):130–135. [PubMed] [Google Scholar]
  29. Polley M. J., Phillips M. L., Wayner E., Nudelman E., Singhal A. K., Hakomori S., Paulson J. C. CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6224–6228. doi: 10.1073/pnas.88.14.6224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shimizu Y., Shaw S., Graber N., Gopal T. V., Horgan K. J., Van Seventer G. A., Newman W. Activation-independent binding of human memory T cells to adhesion molecule ELAM-1. Nature. 1991 Feb 28;349(6312):799–802. doi: 10.1038/349799a0. [DOI] [PubMed] [Google Scholar]
  31. Spertini O., Kansas G. S., Munro J. M., Griffin J. D., Tedder T. F. Regulation of leukocyte migration by activation of the leukocyte adhesion molecule-1 (LAM-1) selectin. Nature. 1991 Feb 21;349(6311):691–694. doi: 10.1038/349691a0. [DOI] [PubMed] [Google Scholar]
  32. Stoolman L. M. Adhesion molecules controlling lymphocyte migration. Cell. 1989 Mar 24;56(6):907–910. doi: 10.1016/0092-8674(89)90620-x. [DOI] [PubMed] [Google Scholar]
  33. Stoolman L. M., Rosen S. D. Possible role for cell-surface carbohydrate-binding molecules in lymphocyte recirculation. J Cell Biol. 1983 Mar;96(3):722–729. doi: 10.1083/jcb.96.3.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tedder T. F., Isaacs C. M., Ernst T. J., Demetri G. D., Adler D. A., Disteche C. M. Isolation and chromosomal localization of cDNAs encoding a novel human lymphocyte cell surface molecule, LAM-1. Homology with the mouse lymphocyte homing receptor and other human adhesion proteins. J Exp Med. 1989 Jul 1;170(1):123–133. doi: 10.1084/jem.170.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tiemeyer M., Swiedler S. J., Ishihara M., Moreland M., Schweingruber H., Hirtzer P., Brandley B. K. Carbohydrate ligands for endothelial-leukocyte adhesion molecule 1. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1138–1142. doi: 10.1073/pnas.88.4.1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. True D. D., Singer M. S., Lasky L. A., Rosen S. D. Requirement for sialic acid on the endothelial ligand of a lymphocyte homing receptor. J Cell Biol. 1990 Dec;111(6 Pt 1):2757–2764. doi: 10.1083/jcb.111.6.2757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tyrrell D., James P., Rao N., Foxall C., Abbas S., Dasgupta F., Nashed M., Hasegawa A., Kiso M., Asa D. Structural requirements for the carbohydrate ligand of E-selectin. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10372–10376. doi: 10.1073/pnas.88.22.10372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Walz G., Aruffo A., Kolanus W., Bevilacqua M., Seed B. Recognition by ELAM-1 of the sialyl-Lex determinant on myeloid and tumor cells. Science. 1990 Nov 23;250(4984):1132–1135. doi: 10.1126/science.1701275. [DOI] [PubMed] [Google Scholar]
  39. Watson S. R., Fennie C., Lasky L. A. Neutrophil influx into an inflammatory site inhibited by a soluble homing receptor-IgG chimaera. Nature. 1991 Jan 10;349(6305):164–167. doi: 10.1038/349164a0. [DOI] [PubMed] [Google Scholar]
  40. Watson S. R., Imai Y., Fennie C., Geoffrey J., Singer M., Rosen S. D., Lasky L. A. The complement binding-like domains of the murine homing receptor facilitate lectin activity. J Cell Biol. 1991 Oct;115(1):235–243. doi: 10.1083/jcb.115.1.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Watson S. R., Imai Y., Fennie C., Geoffroy J. S., Rosen S. D., Lasky L. A. A homing receptor-IgG chimera as a probe for adhesive ligands of lymph node high endothelial venules. J Cell Biol. 1990 Jun;110(6):2221–2229. doi: 10.1083/jcb.110.6.2221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yednock T. A., Stoolman L. M., Rosen S. D. Phosphomannosyl-derivatized beads detect a receptor involved in lymphocyte homing. J Cell Biol. 1987 Mar;104(3):713–723. doi: 10.1083/jcb.104.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]

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