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. 1990 Jun 1;110(6):2221–2229. doi: 10.1083/jcb.110.6.2221

A homing receptor-IgG chimera as a probe for adhesive ligands of lymph node high endothelial venules

PMCID: PMC2116131  PMID: 2190992

Abstract

The binding of lymphocytes to high endothelial venules (HEV) within peripheral lymph nodes (pln) is thought to be mediated by a lectinlike adhesion molecule termed the pln homing receptor (pln HR). The cloning and sequencing of cDNAs encoding both murine and human pln HR revealed that these adhesion molecules contain protein motifs that are homologous to C-type or calcium dependent lectin domains as well as to epidermal growth factor (egf) and complement-regulatory protein domains. We have produced a novel, antibody-like form of the murine HR by joining the extracellular region of the receptor to a human IgG heavy chain. This antibody-like molecule is capable of recognizing carbohydrates, blocking the binding of lymphocytes to pln HEV, and serving as a histochemical reagent for the staining of pln HEV. This murine HR-IgG chimera should prove useful in analyzing the distribution of the HR ligand(s) in normal as well as in inflammatory states.

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Selected References

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  1. 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]
  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. Bonfanti R., Furie B. C., Furie B., Wagner D. D. PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood. 1989 Apr;73(5):1109–1112. [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. Butcher E. C., Scollay R. G., Weissman I. L. Lymphocyte adherence to high endothelial venules: characterization of a modified in vitro assay, and examination of the binding of syngeneic and allogeneic lymphocyte populations. J Immunol. 1979 Nov;123(5):1996–2003. [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. 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]
  10. Chin Y. H., Rasmussen R., Cakiroglu A. G., Woodruff J. J. Lymphocyte recognition of lymph node high endothelium. VI. Evidence of distinct structures mediating binding to high endothelial cells of lymph nodes and Peyer's patches. J Immunol. 1984 Dec;133(6):2961–2965. [PubMed] [Google Scholar]
  11. 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]
  12. Duijvestijn A. M., Schreiber A. B., Butcher E. C. Interferon-gamma regulates an antigen specific for endothelial cells involved in lymphocyte traffic. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9114–9118. doi: 10.1073/pnas.83.23.9114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dustin M. L., Springer T. A. Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol. 1988 Jul;107(1):321–331. doi: 10.1083/jcb.107.1.321. [DOI] [PMC free article] [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. 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]
  17. Haskard D., Cavender D., Beatty P., Springer T., Ziff M. T lymphocyte adhesion to endothelial cells: mechanisms demonstrated by anti-LFA-1 monoclonal antibodies. J Immunol. 1986 Nov 1;137(9):2901–2906. [PubMed] [Google Scholar]
  18. Hendriks H. R., Duijvestijn A. M., Kraal G. Rapid decrease in lymphocyte adherence to high endothelial venules in lymph nodes deprived of afferent lymphatic vessels. Eur J Immunol. 1987 Dec;17(12):1691–1695. doi: 10.1002/eji.1830171203. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Jalkanen S., Steere A. C., Fox R. I., Butcher E. C. A distinct endothelial cell recognition system that controls lymphocyte traffic into inflamed synovium. Science. 1986 Aug 1;233(4763):556–558. doi: 10.1126/science.3726548. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Jutila M. A., Rott L., Berg E. L., Butcher E. C. Function and regulation of the neutrophil MEL-14 antigen in vivo: comparison with LFA-1 and MAC-1. J Immunol. 1989 Nov 15;143(10):3318–3324. [PubMed] [Google Scholar]
  23. Kishimoto T. K., Jutila M. A., Berg E. L., Butcher E. C. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science. 1989 Sep 15;245(4923):1238–1241. doi: 10.1126/science.2551036. [DOI] [PubMed] [Google Scholar]
  24. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987 Sep 11;50(6):975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [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. 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]
  27. 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]
  28. McEver R. P., Beckstead J. H., Moore K. L., Marshall-Carlson L., Bainton D. F. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest. 1989 Jul;84(1):92–99. doi: 10.1172/JCI114175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mountz J. D., Gause W. C., Finkelman F. D., Steinberg A. D. Prevention of lymphadenopathy in MRL-lpr/lpr mice by blocking peripheral lymph node homing with Mel-14 in vivo. J Immunol. 1988 May 1;140(9):2943–2949. [PubMed] [Google Scholar]
  30. Pals S. T., Horst E., Scheper R. J., Meijer C. J. Mechanisms of human lymphocyte migration and their role in the pathogenesis of disease. Immunol Rev. 1989 Apr;108:111–133. doi: 10.1111/j.1600-065x.1989.tb00015.x. [DOI] [PubMed] [Google Scholar]
  31. Reichert R. A., Gallatin W. M., Weissman I. L., Butcher E. C. Germinal center B cells lack homing receptors necessary for normal lymphocyte recirculation. J Exp Med. 1983 Mar 1;157(3):813–827. doi: 10.1084/jem.157.3.813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Sackstein R., Falanga V., Streilein J. W., Chin Y. H. Lymphocyte adhesion to psoriatic dermal endothelium is mediated by a tissue-specific receptor/ligand interaction. J Invest Dermatol. 1988 Nov;91(5):423–428. doi: 10.1111/1523-1747.ep12476441. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. 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]
  37. Smith C. W., Marlin S. D., Rothlein R., Toman C., Anderson D. C. Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J Clin Invest. 1989 Jun;83(6):2008–2017. doi: 10.1172/JCI114111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. 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]
  41. 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]
  42. 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]
  43. 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]
  44. 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]
  45. 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]
  46. 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]
  47. Tonnesen M. G., Anderson D. C., Springer T. A., Knedler A., Avdi N., Henson P. M. Adherence of neutrophils to cultured human microvascular endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1, LFA-1, p150,95 glycoprotein family. J Clin Invest. 1989 Feb;83(2):637–646. doi: 10.1172/JCI113928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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]
  49. Woodruff J. J., Katz M., Lucas L. E., Stamper H. B., Jr An in vitro model of lymphocyte homing. II. Membrane and cytoplasmic events involved in lymphocyte adherence to specialized high-endothelial venules of lymph nodes. J Immunol. 1977 Nov;119(5):1603–1610. [PubMed] [Google Scholar]
  50. 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]
  51. Yednock T. A., Rosen S. D. Lymphocyte homing. Adv Immunol. 1989;44:313–378. doi: 10.1016/s0065-2776(08)60645-8. [DOI] [PubMed] [Google Scholar]
  52. 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]
  53. Zoller M. J., Smith M. Oligonucleotide-directed mutagenesis using M13-derived vectors: an efficient and general procedure for the production of point mutations in any fragment of DNA. Nucleic Acids Res. 1982 Oct 25;10(20):6487–6500. doi: 10.1093/nar/10.20.6487. [DOI] [PMC free article] [PubMed] [Google Scholar]

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