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. 1994 Dec 1;180(6):2219–2226. doi: 10.1084/jem.180.6.2219

Sulfation-dependent recognition of high endothelial venules (HEV)- ligands by L-selectin and MECA 79, and adhesion-blocking monoclonal antibody

PMCID: PMC2191797  PMID: 7525849

Abstract

L-selectin is a lectin-like receptor that mediates the attachment of lymphocytes to high endothelial venules (HEV) of lymph nodes during the process of lymphocyte recirculation. Two sulfated, mucin-like glycoproteins known as Sgp50/GlyCAM-1 and Sgp90/CD34 have previously been identified as HEV-associated ligands for L-selectin. These proteins were originally detected with an L-selectin/Ig chimera called LEC-IgG. GlyCAM-1 and CD34 are also recognized by an antiperipheral node addressin (PNAd) mAb called MECA 79, which blocks L-selectin- dependent adhesion and selectively stains lymph node HEV. The present study compares the requirements for the binding of MECA 79 and LEC-IgG to HEV-ligands. Whereas desialylation of GlyCAM-1 and CD34 drastically reduced binding to LEC-IgG, this treatment enhanced the binding of GlyCAM-1 to MECA 79. In contrast, the binding of both MECA 79 and LEC- IgG to GlyCAM-1 and CD34 was greatly decreased when the sulfation of these ligands was reduced with chlorate, a metabolic inhibitor of sulfation. Because MECA 79 stains HEV-like vessels at various sites of inflammation, recognition by L-selectin of ligands outside of secondary lymphoid organs may depend on sulfation. In addition to their reactivity with GlyCAM-1 and CD34, both MECA 79 and LEC-IgG recognize an independent molecule of approximately 200 kD in a sulfate-dependent manner. Thus, this molecule, which we designate Sgp200, is an additional ligand for L-selectin.

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Selected References

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  1. Andrews P., Milsom D. W., Ford W. L. Migration of lymphocytes across specialized vascular endothelium. V. Production of a sulphated macromolecule by high endothelial cells in lymph nodes. J Cell Sci. 1982 Oct;57:277–292. doi: 10.1242/jcs.57.1.277. [DOI] [PubMed] [Google Scholar]
  2. Arbonés M. L., Ord D. C., Ley K., Ratech H., Maynard-Curry C., Otten G., Capon D. J., Tedder T. F. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity. 1994 Jul;1(4):247–260. doi: 10.1016/1074-7613(94)90076-0. [DOI] [PubMed] [Google Scholar]
  3. Baumheter S., Singer M. S., Henzel W., Hemmerich S., Renz M., Rosen S. D., Lasky L. A. Binding of L-selectin to the vascular sialomucin CD34. Science. 1993 Oct 15;262(5132):436–438. doi: 10.1126/science.7692600. [DOI] [PubMed] [Google Scholar]
  4. Berg E. L., Magnani J., Warnock R. A., Robinson M. K., Butcher E. C. Comparison of L-selectin and E-selectin ligand specificities: the L-selectin can bind the E-selectin ligands sialyl Le(x) and sialyl Le(a). Biochem Biophys Res Commun. 1992 Apr 30;184(2):1048–1055. doi: 10.1016/0006-291x(92)90697-j. [DOI] [PubMed] [Google Scholar]
  5. Berg E. L., McEvoy L. M., Berlin C., Bargatze R. F., Butcher E. C. L-selectin-mediated lymphocyte rolling on MAdCAM-1. Nature. 1993 Dec 16;366(6456):695–698. doi: 10.1038/366695a0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Berlin C., Berg E. L., Briskin M. J., Andrew D. P., Kilshaw P. J., Holzmann B., Weissman I. L., Hamann A., Butcher E. C. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell. 1993 Jul 16;74(1):185–195. doi: 10.1016/0092-8674(93)90305-a. [DOI] [PubMed] [Google Scholar]
  8. Bevilacqua M. P., Nelson R. M. Selectins. J Clin Invest. 1993 Feb;91(2):379–387. doi: 10.1172/JCI116210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Briskin M. J., McEvoy L. M., Butcher E. C. MAdCAM-1 has homology to immunoglobulin and mucin-like adhesion receptors and to IgA1. Nature. 1993 Jun 3;363(6428):461–464. doi: 10.1038/363461a0. [DOI] [PubMed] [Google Scholar]
  10. Brustein M., Kraal G., Mebius R. E., Watson S. R. Identification of a soluble form of a ligand for the lymphocyte homing receptor. J Exp Med. 1992 Nov 1;176(5):1415–1419. doi: 10.1084/jem.176.5.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  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. Faveeuw C., Gagnerault M. C., Lepault F. Expression of homing and adhesion molecules in infiltrated islets of Langerhans and salivary glands of nonobese diabetic mice. J Immunol. 1994 Jun 15;152(12):5969–5978. [PubMed] [Google Scholar]
  14. Foxall C., Watson S. R., Dowbenko D., Fennie C., Lasky L. A., Kiso M., Hasegawa A., Asa D., Brandley B. K. The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide. J Cell Biol. 1992 May;117(4):895–902. doi: 10.1083/jcb.117.4.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Freemont A. J. Molecules controlling lymphocyte-endothelial interactions in lymph nodes are produced in vessels of inflamed synovium. Ann Rheum Dis. 1987 Dec;46(12):924–928. doi: 10.1136/ard.46.12.924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Greaves M. F., Brown J., Molgaard H. V., Spurr N. K., Robertson D., Delia D., Sutherland D. R. Molecular features of CD34: a hemopoietic progenitor cell-associated molecule. Leukemia. 1992;6 (Suppl 1):31–36. [PubMed] [Google Scholar]
  17. Green P. J., Tamatani T., Watanabe T., Miyasaka M., Hasegawa A., Kiso M., Yuen C. T., Stoll M. S., Feizi T. High affinity binding of the leucocyte adhesion molecule L-selectin to 3'-sulphated-Le(a) and -Le(x) oligosaccharides and the predominance of sulphate in this interaction demonstrated by binding studies with a series of lipid-linked oligosaccharides. Biochem Biophys Res Commun. 1992 Oct 15;188(1):244–251. doi: 10.1016/0006-291x(92)92376-9. [DOI] [PubMed] [Google Scholar]
  18. Hamann A., Andrew D. P., Jablonski-Westrich D., Holzmann B., Butcher E. C. Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol. 1994 Apr 1;152(7):3282–3293. [PubMed] [Google Scholar]
  19. Hemmerich S., Bertozzi C. R., Leffler H., Rosen S. D. Identification of the sulfated monosaccharides of GlyCAM-1, an endothelial-derived ligand for L-selectin. Biochemistry. 1994 Apr 26;33(16):4820–4829. doi: 10.1021/bi00182a010. [DOI] [PubMed] [Google Scholar]
  20. Hemmerich S., Rosen S. D. 6'-sulfated sialyl Lewis x is a major capping group of GlyCAM-1. Biochemistry. 1994 Apr 26;33(16):4830–4835. doi: 10.1021/bi00182a011. [DOI] [PubMed] [Google Scholar]
  21. Higuchi Y., Herrera P., Muniesa P., Huarte J., Belin D., Ohashi P., Aichele P., Orci L., Vassalli J. D., Vassalli P. Expression of a tumor necrosis factor alpha transgene in murine pancreatic beta cells results in severe and permanent insulitis without evolution towards diabetes. J Exp Med. 1992 Dec 1;176(6):1719–1731. doi: 10.1084/jem.176.6.1719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Huang K., Kikuta A., Rosen S. D. Myelin localization of a central nervous system ligand for L-selectin. J Neuroimmunol. 1994 Sep;53(2):133–141. doi: 10.1016/0165-5728(94)90023-x. [DOI] [PubMed] [Google Scholar]
  23. Hänninen A., Taylor C., Streeter P. R., Stark L. S., Sarte J. M., Shizuru J. A., Simell O., Michie S. A. Vascular addressins are induced on islet vessels during insulitis in nonobese diabetic mice and are involved in lymphoid cell binding to islet endothelium. J Clin Invest. 1993 Nov;92(5):2509–2515. doi: 10.1172/JCI116859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Imai Y., Lasky L. A., Rosen S. D. Further characterization of the interaction between L-selectin and its endothelial ligands. Glycobiology. 1992 Aug;2(4):373–381. doi: 10.1093/glycob/2.4.373. [DOI] [PubMed] [Google Scholar]
  25. Imai Y., Lasky L. A., Rosen S. D. Sulphation requirement for GlyCAM-1, an endothelial ligand for L-selectin. Nature. 1993 Feb 11;361(6412):555–557. doi: 10.1038/361555a0. [DOI] [PubMed] [Google Scholar]
  26. Imai Y., Rosen S. D. Direct demonstration of heterogeneous, sulfated O-linked carbohydrate chains on an endothelial ligand for L-selectin. Glycoconj J. 1993 Feb;10(1):34–39. doi: 10.1007/BF00731184. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  30. Larsen G. R., Sako D., Ahern T. J., Shaffer M., Erban J., Sajer S. A., Gibson R. M., Wagner D. D., Furie B. C., Furie B. P-selectin and E-selectin. Distinct but overlapping leukocyte ligand specificities. J Biol Chem. 1992 Jun 5;267(16):11104–11110. [PubMed] [Google Scholar]
  31. Lasky L. A. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science. 1992 Nov 6;258(5084):964–969. doi: 10.1126/science.1439808. [DOI] [PubMed] [Google Scholar]
  32. Lasky L. A., Singer M. S., Dowbenko D., Imai Y., Henzel W. J., Grimley C., Fennie C., Gillett N., Watson S. R., Rosen S. D. An endothelial ligand for L-selectin is a novel mucin-like molecule. Cell. 1992 Jun 12;69(6):927–938. doi: 10.1016/0092-8674(92)90612-g. [DOI] [PubMed] [Google Scholar]
  33. Lee M. S., Sarvetnick N. Induction of vascular addressins and adhesion molecules in the pancreas of IFN-gamma transgenic mice. J Immunol. 1994 May 1;152(9):4597–4603. [PubMed] [Google Scholar]
  34. Lewinsohn D. M., Bargatze R. F., Butcher E. C. Leukocyte-endothelial cell recognition: evidence of a common molecular mechanism shared by neutrophils, lymphocytes, and other leukocytes. J Immunol. 1987 Jun 15;138(12):4313–4321. [PubMed] [Google Scholar]
  35. Luscinskas F. W., Kansas G. S., Ding H., Pizcueta P., Schleiffenbaum B. E., Tedder T. F., Gimbrone M. A., Jr Monocyte rolling, arrest and spreading on IL-4-activated vascular endothelium under flow is mediated via sequential action of L-selectin, beta 1-integrins, and beta 2-integrins. J Cell Biol. 1994 Jun;125(6):1417–1427. doi: 10.1083/jcb.125.6.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Mackay C. R., Marston W., Dudler L. Altered patterns of T cell migration through lymph nodes and skin following antigen challenge. Eur J Immunol. 1992 Sep;22(9):2205–2210. doi: 10.1002/eji.1830220904. [DOI] [PubMed] [Google Scholar]
  37. Mebius R. E., Watson S. R. L- and E-selectin can recognize the same naturally occurring ligands on high endothelial venules. J Immunol. 1993 Sep 15;151(6):3252–3260. [PubMed] [Google Scholar]
  38. Michie S. A., Streeter P. R., Bolt P. A., Butcher E. C., Picker L. J. The human peripheral lymph node vascular addressin. An inducible endothelial antigen involved in lymphocyte homing. Am J Pathol. 1993 Dec;143(6):1688–1698. [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Needham L. K., Schnaar R. L. The HNK-1 reactive sulfoglucuronyl glycolipids are ligands for L-selectin and P-selectin but not E-selectin. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1359–1363. doi: 10.1073/pnas.90.4.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Norgard-Sumnicht K. E., Varki N. M., Varki A. Calcium-dependent heparin-like ligands for L-selectin in nonlymphoid endothelial cells. Science. 1993 Jul 23;261(5120):480–483. doi: 10.1126/science.7687382. [DOI] [PubMed] [Google Scholar]
  42. Paavonen T., Renkonen R. Selective expression of sialyl-Lewis x and Lewis a epitopes, putative ligands for L-selectin, on peripheral lymph-node high endothelial venules. Am J Pathol. 1992 Dec;141(6):1259–1264. [PMC free article] [PubMed] [Google Scholar]
  43. Rosen S. D., Bertozzi C. R. The selectins and their ligands. Curr Opin Cell Biol. 1994 Oct;6(5):663–673. doi: 10.1016/0955-0674(94)90092-2. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. 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]
  46. Sako D., Chang X. J., Barone K. M., Vachino G., White H. M., Shaw G., Veldman G. M., Bean K. M., Ahern T. J., Furie B. Expression cloning of a functional glycoprotein ligand for P-selectin. Cell. 1993 Dec 17;75(6):1179–1186. doi: 10.1016/0092-8674(93)90327-m. [DOI] [PubMed] [Google Scholar]
  47. Salmi M., Granfors K., MacDermott R., Jalkanen S. Aberrant binding of lamina propria lymphocytes to vascular endothelium in inflammatory bowel diseases. Gastroenterology. 1994 Mar;106(3):596–605. doi: 10.1016/0016-5085(94)90691-2. [DOI] [PubMed] [Google Scholar]
  48. Sawada M., Takada A., Ohwaki I., Takahashi N., Tateno H., Sakamoto J., Kannagi R. Specific expression of a complex sialyl Lewis X antigen on high endothelial venules of human lymph nodes: possible candidate for L-selectin ligand. Biochem Biophys Res Commun. 1993 May 28;193(1):337–347. doi: 10.1006/bbrc.1993.1629. [DOI] [PubMed] [Google Scholar]
  49. Springer T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994 Jan 28;76(2):301–314. doi: 10.1016/0092-8674(94)90337-9. [DOI] [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. 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]
  52. Suzuki Y., Toda Y., Tamatani T., Watanabe T., Suzuki T., Nakao T., Murase K., Kiso M., Hasegawa A., Tadano-Aritomi K. Sulfated glycolipids are ligands for a lymphocyte homing receptor, L-selectin (LECAM-1), Binding epitope in sulfated sugar chain. Biochem Biophys Res Commun. 1993 Jan 29;190(2):426–434. doi: 10.1006/bbrc.1993.1065. [DOI] [PubMed] [Google Scholar]
  53. Tamatani T., Kuida K., Watanabe T., Koike S., Miyasaka M. Molecular mechanisms underlying lymphocyte recirculation. III. Characterization of the LECAM-1 (L-selectin)-dependent adhesion pathway in rats. J Immunol. 1993 Mar 1;150(5):1735–1745. [PubMed] [Google Scholar]
  54. 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]
  55. Weissman I. L. Developmental switches in the immune system. Cell. 1994 Jan 28;76(2):207–218. doi: 10.1016/0092-8674(94)90329-8. [DOI] [PubMed] [Google Scholar]
  56. Wogensen L., Huang X., Sarvetnick N. Leukocyte extravasation into the pancreatic tissue in transgenic mice expressing interleukin 10 in the islets of Langerhans. J Exp Med. 1993 Jul 1;178(1):175–185. doi: 10.1084/jem.178.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Yamashita K., Kochibe N., Ohkura T., Ueda I., Kobata A. Fractionation of L-fucose-containing oligosaccharides on immobilized Aleuria aurantia lectin. J Biol Chem. 1985 Apr 25;260(8):4688–4693. [PubMed] [Google Scholar]

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