Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1990 Dec 1;111(6):2757–2764. doi: 10.1083/jcb.111.6.2757

Requirement for sialic acid on the endothelial ligand of a lymphocyte homing receptor

PMCID: PMC2116434  PMID: 2277086

Abstract

The entry of blood-borne lymphocytes into most secondary lymphoid organs is initiated by a highly specific adhesive interaction with the specialized cuboidal endothelial cells of high endothelial venules (HEV). The adhesive receptors on lymphocytes that dictate interactions with HEV in different lymphoid organs are called homing receptors, signifying their critical role in controlling organ-selective lymphocyte migration. Considerable work has established that the mouse peripheral lymph node homing receptor (pnHR), defined by the mAb MEL- 14, functions as a lectin-like adhesive protein. We have previously shown that sialidase treatment of peripheral lymph node (PN) HEV abrogates lymphocyte attachment to the HEV both in vivo and in vitro. We extend this evidence by demonstrating that Limax agglutinin (LA), a sialic acid-specific lectin, when reacted with HEV exposed in cryostat- cut tissue sections, blocks lymphocyte attachment to PN HEV and, unexpectedly, to the HEV of Peyer's patches (PP) as well. Using a recombinant form of the pnHR as a histochemical probe for its cognate adhesive site (HEV-ligand) on PN HEV, we demonstrate that both sialidase and Limax agglutinin functionally inactive this ligand. It is concluded that the requirement for sialic acid is at the level of the pnHR interaction with its HEV ligand. A distinct sialyloligosaccharide may encode the recognition determinant of a PP HEV ligand.

Full Text

The Full Text of this article is available as a PDF (5.8 MB).

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., 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]
  3. Bhavanandan V. P., Katlic A. W. The interaction of wheat germ agglutinin with sialoglycoproteins. The role of sialic acid. J Biol Chem. 1979 May 25;254(10):4000–4008. [PubMed] [Google Scholar]
  4. Bowen B. R., Fennie C., Lasky L. A. The Mel 14 antibody binds to the lectin domain of the murine peripheral lymph node homing receptor. J Cell Biol. 1990 Jan;110(1):147–153. doi: 10.1083/jcb.110.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bowen B. R., Nguyen T., Lasky L. A. Characterization of a human homologue of the murine peripheral lymph node homing receptor. J Cell Biol. 1989 Jul;109(1):421–427. doi: 10.1083/jcb.109.1.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. 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]
  9. Butcher E. C. Warner-Lambert/Parke-Davis Award lecture. Cellular and molecular mechanisms that direct leukocyte traffic. Am J Pathol. 1990 Jan;136(1):3–11. [PMC free article] [PubMed] [Google Scholar]
  10. Camerini D., James S. P., Stamenkovic I., Seed B. Leu-8/TQ1 is the human equivalent of the Mel-14 lymph node homing receptor. Nature. 1989 Nov 2;342(6245):78–82. doi: 10.1038/342078a0. [DOI] [PubMed] [Google Scholar]
  11. Chin Y. H., Rasmussen R. A., Woodruff J. J., Easton T. G. A monoclonal anti-HEBFPP antibody with specificity for lymphocyte surface molecules mediating adhesion to Peyer's patch high endothelium of the rat. J Immunol. 1986 Apr 1;136(7):2556–2561. [PubMed] [Google Scholar]
  12. Drickamer K. Two distinct classes of carbohydrate-recognition domains in animal lectins. J Biol Chem. 1988 Jul 15;263(20):9557–9560. [PubMed] [Google Scholar]
  13. Duijvestijn A., Hamann A. Mechanisms and regulation of lymphocyte migration. Immunol Today. 1989 Jan;10(1):23–28. doi: 10.1016/0167-5699(89)90061-3. [DOI] [PubMed] [Google Scholar]
  14. Gallatin M., St John T. P., Siegelman M., Reichert R., Butcher E. C., Weissman I. L. Lymphocyte homing receptors. Cell. 1986 Mar 14;44(5):673–680. doi: 10.1016/0092-8674(86)90832-9. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Geng J. G., Bevilacqua M. P., Moore K. L., McIntyre T. M., Prescott S. M., Kim J. M., Bliss G. A., Zimmerman G. A., McEver R. P. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature. 1990 Feb 22;343(6260):757–760. doi: 10.1038/343757a0. [DOI] [PubMed] [Google Scholar]
  17. Geoffroy J. S., Rosen S. D. Demonstration that a lectin-like receptor (gp90MEL) directly mediates adhesion of lymphocytes to high endothelial venules of lymph nodes. J Cell Biol. 1989 Nov;109(5):2463–2469. doi: 10.1083/jcb.109.5.2463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Goldstein L. A., Zhou D. F., Picker L. J., Minty C. N., Bargatze R. F., Ding J. F., Butcher E. C. A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins. Cell. 1989 Mar 24;56(6):1063–1072. doi: 10.1016/0092-8674(89)90639-9. [DOI] [PubMed] [Google Scholar]
  19. Hamann A., Jablonski-Westrich D., Duijvestijn A., Butcher E. C., Baisch H., Harder R., Thiele H. G. Evidence for an accessory role of LFA-1 in lymphocyte-high endothelium interaction during homing. J Immunol. 1988 Feb 1;140(3):693–699. [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Jalkanen S. T., Bargatze R. F., Herron L. R., Butcher E. C. A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man. Eur J Immunol. 1986 Oct;16(10):1195–1202. doi: 10.1002/eji.1830161003. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. 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]
  26. Lis H., Sharon N. Lectins as molecules and as tools. Annu Rev Biochem. 1986;55:35–67. doi: 10.1146/annurev.bi.55.070186.000343. [DOI] [PubMed] [Google Scholar]
  27. Magnani J. L. Mouse and rat monoclonal antibodies directed against carbohydrates. Methods Enzymol. 1987;138:484–491. doi: 10.1016/0076-6879(87)38041-3. [DOI] [PubMed] [Google Scholar]
  28. Michalek M. T., Bremer E. G., Mold C. Effect of gangliosides on activation of the alternative pathway of human complement. J Immunol. 1988 Mar 1;140(5):1581–1587. [PubMed] [Google Scholar]
  29. Michalek M. T., Mold C., Bremer E. G. Inhibition of the alternative pathway of human complement by structural analogues of sialic acid. J Immunol. 1988 Mar 1;140(5):1588–1594. [PubMed] [Google Scholar]
  30. Miller R. L., Collawn J. F., Jr, Fish W. W. Purification and macromolecular properties of a sialic acid-specific lectin from the slug Limax flavus. J Biol Chem. 1982 Jul 10;257(13):7574–7580. [PubMed] [Google Scholar]
  31. Miller R. L. Properties of a sialic acid-specific lectin from the slug Limax flavus. Methods Enzymol. 1987;138:527–536. doi: 10.1016/0076-6879(87)38047-4. [DOI] [PubMed] [Google Scholar]
  32. Molin K., Fredman P., Svennerholm L. Binding specificities of the lectins PNA, WGA and UEA I to polyvinylchloride-adsorbed glycosphingolipids. FEBS Lett. 1986 Sep 1;205(1):51–55. doi: 10.1016/0014-5793(86)80864-x. [DOI] [PubMed] [Google Scholar]
  33. Nicolson G. L. The interactions of lectins with animal cell surfaces. Int Rev Cytol. 1974;39:89–190. doi: 10.1016/s0074-7696(08)60939-0. [DOI] [PubMed] [Google Scholar]
  34. Pals S. T., den Otter A., Miedema F., Kabel P., Keizer G. D., Scheper R. J., Meijer C. J. Evidence that leukocyte function-associated antigen-1 is involved in recirculation and homing of human lymphocytes via high endothelial venules. J Immunol. 1988 Mar 15;140(6):1851–1853. [PubMed] [Google Scholar]
  35. Ravindranath M. H., Higa H. H., Cooper E. L., Paulson J. C. Purification and characterization of an O-acetylsialic acid-specific lectin from a marine crab Cancer antennarius. J Biol Chem. 1985 Jul 25;260(15):8850–8856. [PubMed] [Google Scholar]
  36. 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]
  37. Rosen S. D. Lymphocyte homing: progress and prospects. Curr Opin Cell Biol. 1989 Oct;1(5):913–919. doi: 10.1016/0955-0674(89)90058-6. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Rosen S. D., Yednock T. A. Lymphocyte attachment to high endothelial venules during recirculation: a possible role for carbohydrates as recognition determinants. Mol Cell Biochem. 1986 Nov-Dec;72(1-2):153–164. doi: 10.1007/BF00230642. [DOI] [PubMed] [Google Scholar]
  40. Schauer R. Chemistry, metabolism, and biological functions of sialic acids. Adv Carbohydr Chem Biochem. 1982;40:131–234. doi: 10.1016/s0065-2318(08)60109-2. [DOI] [PubMed] [Google Scholar]
  41. Schulte B. A., Spicer S. S., Miller R. L. Histochemical localization of sialoglycoconjugates with a sialic acid-specific lectin from the slug Limax flavus. Histochem J. 1984 Oct;16(10):1125–1132. doi: 10.1007/BF01002899. [DOI] [PubMed] [Google Scholar]
  42. Sharon N., Lis H. Lectins as cell recognition molecules. Science. 1989 Oct 13;246(4927):227–234. doi: 10.1126/science.2552581. [DOI] [PubMed] [Google Scholar]
  43. Siegelman M. H., Cheng I. C., Weissman I. L., Wakeland E. K. The mouse lymph node homing receptor is identical with the lymphocyte cell surface marker Ly-22: role of the EGF domain in endothelial binding. Cell. 1990 May 18;61(4):611–622. doi: 10.1016/0092-8674(90)90473-r. [DOI] [PubMed] [Google Scholar]
  44. Siegelman M. H., Weissman I. L. Human homologue of mouse lymph node homing receptor: evolutionary conservation at tandem cell interaction domains. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5562–5566. doi: 10.1073/pnas.86.14.5562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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]
  46. Stamenkovic I., Amiot M., Pesando J. M., Seed B. A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell. 1989 Mar 24;56(6):1057–1062. doi: 10.1016/0092-8674(89)90638-7. [DOI] [PubMed] [Google Scholar]
  47. Stamper H. B., Jr, Woodruff J. J. Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity of recirculating lymphocytes for high-endothelial venules. J Exp Med. 1976 Sep 1;144(3):828–833. doi: 10.1084/jem.144.3.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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]
  49. 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]
  50. 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]
  51. 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]
  52. 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]
  53. 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]
  54. 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]
  55. 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]
  56. Tedder T. F., Penta A. C., Levine H. B., Freedman A. S. Expression of the human leukocyte adhesion molecule, LAM1. Identity with the TQ1 and Leu-8 differentiation antigens. J Immunol. 1990 Jan 15;144(2):532–540. [PubMed] [Google Scholar]
  57. Wagner P., Roth J. Occurrence and distribution of sialic acid residues in developing rat glomerulus: investigations with the Limax flavus and the wheat germ agglutinin. Eur J Cell Biol. 1988 Dec;47(2):259–269. [PubMed] [Google Scholar]
  58. 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]
  59. Wiley D. C., Skehel J. J. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem. 1987;56:365–394. doi: 10.1146/annurev.bi.56.070187.002053. [DOI] [PubMed] [Google Scholar]
  60. Woodruff J. J., Clarke L. M., Chin Y. H. Specific cell-adhesion mechanisms determining migration pathways of recirculating lymphocytes. Annu Rev Immunol. 1987;5:201–222. doi: 10.1146/annurev.iy.05.040187.001221. [DOI] [PubMed] [Google Scholar]
  61. 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]
  62. 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]

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

RESOURCES