Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1991 Jul 2;114(2):343–349. doi: 10.1083/jcb.114.2.343

The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor

PMCID: PMC2289069  PMID: 1712790

Abstract

The trafficking of lymphocytes from the blood and into lymphoid organs is controlled by tissue-selective lymphocyte interactions with specialized endothelial cells lining post capillary venules, in particular the high endothelial venules (HEV) found in lymphoid tissues and sites of chronic inflammation. Lymphocyte interactions with HEV are mediated in part by lymphocyte homing receptors and tissue-specific HEV determinants, the vascular addressins. A peripheral lymph node addressin (PNAd) has been detected immunohistologically in mouse and man by monoclonal antibody MECA-79, which inhibits lymphocyte homing to lymph nodes and lymphocyte binding to lymph node and tonsillar HEV. The human MECA-79 antigen, PNAd, is molecularly distinct from the 65-kD mucosal vascular addressin. The most abundant iodinated species by SDS- PAGE is 105 kD. When affinity isolated and immobilized on glass slides, MECA-79 immunoisolated material binds human and mouse lymphocytes avidly in a calcium dependent manner. Binding is blocked by mAb MECA- 79, by antibodies against mouse or human LECAM-1 (the peripheral lymph node homing receptor, the MEL-14 antigen, LAM-1), and by treatment of PNAd with neuraminidase. Expression of LECAM-1 cDNA confers PNAd binding ability on a transfected B cell line. We conclude that LECAM-1 mediates lymphocyte binding to PNAd, an interaction that involves the lectin activity of LECAM-1 and carbohydrate determinants on the addressin.

Full Text

The Full Text of this article is available as a PDF (803.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berg E. L., Goldstein L. A., Jutila M. A., Nakache M., Picker L. J., Streeter P. R., Wu N. W., Zhou D., Butcher E. C. Homing receptors and vascular addressins: cell adhesion molecules that direct lymphocyte traffic. Immunol Rev. 1989 Apr;108:5–18. doi: 10.1111/j.1600-065x.1989.tb00010.x. [DOI] [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. Butcher E. C., Scollay R. G., Weissman I. L. Organ specificity of lymphocyte migration: mediation by highly selective lymphocyte interaction with organ-specific determinants on high endothelial venules. Eur J Immunol. 1980 Jul;10(7):556–561. doi: 10.1002/eji.1830100713. [DOI] [PubMed] [Google Scholar]
  5. Butcher E. C. The regulation of lymphocyte traffic. Curr Top Microbiol Immunol. 1986;128:85–122. doi: 10.1007/978-3-642-71272-2_3. [DOI] [PubMed] [Google Scholar]
  6. Chin Y. H., Falanga V., Streilein J. W., Sackstein R. Specific lymphocyte-endothelial cell interactions regulate migration into lymph nodes, Peyer's patches, and skin. Reg Immunol. 1988 Jul-Aug;1(1):78–83. [PubMed] [Google Scholar]
  7. Corral L., Singer M. S., Macher B. A., Rosen S. D. Requirement for sialic acid on neutrophils in a GMP-140 (PADGEM) mediated adhesive interaction with activated platelets. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1349–1356. doi: 10.1016/0006-291x(90)91598-m. [DOI] [PubMed] [Google Scholar]
  8. Duijvestijn A. M., Horst E., Pals S. T., Rouse B. N., Steere A. C., Picker L. J., Meijer C. J., Butcher E. C. High endothelial differentiation in human lymphoid and inflammatory tissues defined by monoclonal antibody HECA-452. Am J Pathol. 1988 Jan;130(1):147–155. [PMC free article] [PubMed] [Google Scholar]
  9. GOWANS J. L., KNIGHT E. J. THE ROUTE OF RE-CIRCULATION OF LYMPHOCYTES IN THE RAT. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:257–282. doi: 10.1098/rspb.1964.0001. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Goelz S. E., Hession C., Goff D., Griffiths B., Tizard R., Newman B., Chi-Rosso G., Lobb R. ELFT: a gene that directs the expression of an ELAM-1 ligand. Cell. 1990 Dec 21;63(6):1349–1356. doi: 10.1016/0092-8674(90)90430-m. [DOI] [PubMed] [Google Scholar]
  12. Holzmann B., McIntyre B. W., Weissman I. L. Identification of a murine Peyer's patch--specific lymphocyte homing receptor as an integrin molecule with an alpha chain homologous to human VLA-4 alpha. Cell. 1989 Jan 13;56(1):37–46. doi: 10.1016/0092-8674(89)90981-1. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Jalkanen S., Bargatze R. F., de los Toyos J., Butcher E. C. Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells. J Cell Biol. 1987 Aug;105(2):983–990. doi: 10.1083/jcb.105.2.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Kishimoto T. K., Jutila M. A., Butcher E. C. Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2244–2248. doi: 10.1073/pnas.87.6.2244. [DOI] [PMC free article] [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. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. MARCHESI V. T., GOWANS J. L. THE MIGRATION OF LYMPHOCYTES THROUGH THE ENDOTHELIUM OF VENULES IN LYMPH NODES: AN ELECTRON MICROSCOPE STUDY. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:283–290. doi: 10.1098/rspb.1964.0002. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Mulligan R. C., Berg P. Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2072–2076. doi: 10.1073/pnas.78.4.2072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nakache M., Berg E. L., Streeter P. R., Butcher E. C. The mucosal vascular addressin is a tissue-specific endothelial cell adhesion molecule for circulating lymphocytes. Nature. 1989 Jan 12;337(6203):179–181. doi: 10.1038/337179a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Picker L. J., Michie S. A., Rott L. S., Butcher E. C. A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol. 1990 May;136(5):1053–1068. [PMC free article] [PubMed] [Google Scholar]
  27. Picker L. J., Terstappen L. W., Rott L. S., Streeter P. R., Stein H., Butcher E. C. Differential expression of homing-associated adhesion molecules by T cell subsets in man. J Immunol. 1990 Nov 15;145(10):3247–3255. [PubMed] [Google Scholar]
  28. Rosen S. D., Chi S. I., True D. D., Singer M. S., Yednock T. A. Intravenously injected sialidase inactivates attachment sites for lymphocytes on high endothelial venules. J Immunol. 1989 Mar 15;142(6):1895–1902. [PubMed] [Google Scholar]
  29. Rosen S. D., Singer M. S., Yednock T. A., Stoolman L. M. Involvement of sialic acid on endothelial cells in organ-specific lymphocyte recirculation. Science. 1985 May 24;228(4702):1005–1007. doi: 10.1126/science.4001928. [DOI] [PubMed] [Google Scholar]
  30. Sarmiento M., Dialynas D. P., Lancki D. W., Wall K. A., Lorber M. I., Loken M. R., Fitch F. W. Cloned T lymphocytes and monoclonal antibodies as probes for cell surface molecules active in T cell-mediated cytolysis. Immunol Rev. 1982;68:135–169. doi: 10.1111/j.1600-065x.1982.tb01063.x. [DOI] [PubMed] [Google Scholar]
  31. Siegelman M. H., van de Rijn M., Weissman I. L. Mouse lymph node homing receptor cDNA clone encodes a glycoprotein revealing tandem interaction domains. Science. 1989 Mar 3;243(4895):1165–1172. doi: 10.1126/science.2646713. [DOI] [PubMed] [Google Scholar]
  32. Stephens P. E., Cockett M. I. The construction of a highly efficient and versatile set of mammalian expression vectors. Nucleic Acids Res. 1989 Sep 12;17(17):7110–7110. doi: 10.1093/nar/17.17.7110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Stoolman L. M., Ebling H. Adhesion molecules of cultured hematopoietic malignancies. A calcium-dependent lectin is the principle mediator of binding to the high endothelial venule of lymph nodes. J Clin Invest. 1989 Oct;84(4):1196–1205. doi: 10.1172/JCI114285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Stoolman L. M., Tenforde T. S., Rosen S. D. Phosphomannosyl receptors may participate in the adhesive interaction between lymphocytes and high endothelial venules. J Cell Biol. 1984 Oct;99(4 Pt 1):1535–1540. doi: 10.1083/jcb.99.4.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stoolman L. M., Yednock T. A., Rosen S. D. Homing receptors on human and rodent lymphocytes--evidence for a conserved carbohydrate-binding specificity. Blood. 1987 Dec;70(6):1842–1850. [PubMed] [Google Scholar]
  37. Streeter P. R., Berg E. L., Rouse B. T., Bargatze R. F., Butcher E. C. A tissue-specific endothelial cell molecule involved in lymphocyte homing. Nature. 1988 Jan 7;331(6151):41–46. doi: 10.1038/331041a0. [DOI] [PubMed] [Google Scholar]
  38. Streeter P. R., Rouse B. T., Butcher E. C. Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes. J Cell Biol. 1988 Nov;107(5):1853–1862. doi: 10.1083/jcb.107.5.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. 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]
  41. Wu N. W., Jalkanen S., Streeter P. R., Butcher E. C. Evolutionary conservation of tissue-specific lymphocyte-endothelial cell recognition mechanisms involved in lymphocyte homing. J Cell Biol. 1988 Nov;107(5):1845–1851. doi: 10.1083/jcb.107.5.1845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yednock T. A., Butcher E. C., Stoolman L. M., Rosen S. D. Receptors involved in lymphocyte homing: relationship between a carbohydrate-binding receptor and the MEL-14 antigen. J Cell Biol. 1987 Mar;104(3):725–731. doi: 10.1083/jcb.104.3.725. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES