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. 1996 Nov;89(3):375–383. doi: 10.1046/j.1365-2567.1996.d01-750.x

Expression of VCAM-1 and VLA-4 dependent T-lymphocyte adhesion to dermal fibroblasts stimulated with proinflammatory cytokines.

J X Gao 1, A C Issekutz 1
PMCID: PMC1456543  PMID: 8958050

Abstract

In chronic inflammatory conditions, mononuclear cells infiltrate the involved connective tissue and may persist, perhaps because of binding to adhesion molecules on connective tissue cells, as well as extracellular matrix. Here we investigated whether vascular cell adhesion molecule-1 (VCAM-1) may be induced on human dermal fibroblasts by proinflammatory cytokines. Expression of VCAM-1 was determined by Northern blotting, cell enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Only trace amounts of VCAM-1 mRNA or protein were constitutively expressed on dermal fibroblasts but both were rapidly (within 4 hr) upregulated by tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) and somewhat slower (20 hr) by interferon-gamma (IFN-gamma). The combination of TNF-alpha and IFN-gamma had at least an additive effect. The adhesion function of the expressed VCAM-1 was examined by studying the adhesion of the Jurkat T lymphocytes to fibroblasts. Adhesion of Jurkat cells to dermal fibroblasts was markedly increased by stimulation of fibroblasts with TNF-alpha and IFN-gamma (22% of cells adhered versus 9% on unstimulated fibroblasts). The increased adhesion was inhibited to that on unstimulated fibroblasts by monoclonal antibody (mAb) to domain 1 of VCAM-1, but not by mAb to domain 4. MAb to very late antigen-4 (VLA-4), the integrin counter-receptor on lymphocytes for VCAM-1, completely inhibited the increase in Jurkat cell adhesion to activated fibroblasts and partly also inhibited basal adhesion to unstimulated fibroblasts. These results suggest that VCAM-1 expression by dermal fibroblasts is inducible at the mRNA, protein and functional levels by proinflammatory cytokines. The VLA-4/VCAM-1 pathway maybe involved in adhesive interactions between T lymphocytes and activated fibroblasts in the skin during chronic dermal inflammatory conditions.

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Selected References

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  1. Argenbright L. W., Letts L. G., Rothlein R. Monoclonal antibodies to the leukocyte membrane CD18 glycoprotein complex and to intercellular adhesion molecule-1 inhibit leukocyte-endothelial adhesion in rabbits. J Leukoc Biol. 1991 Mar;49(3):253–257. doi: 10.1002/jlb.49.3.253. [DOI] [PubMed] [Google Scholar]
  2. Bohnsack J. F. CD11/CD18-independent neutrophil adherence to laminin is mediated by the integrin VLA-6. Blood. 1992 Mar 15;79(6):1545–1552. [PubMed] [Google Scholar]
  3. Bombara M. P., Webb D. L., Conrad P., Marlor C. W., Sarr T., Ranges G. E., Aune T. M., Greve J. M., Blue M. L. Cell contact between T cells and synovial fibroblasts causes induction of adhesion molecules and cytokines. J Leukoc Biol. 1993 Nov;54(5):399–406. doi: 10.1002/jlb.54.5.399. [DOI] [PubMed] [Google Scholar]
  4. Cabañas C., Hogg N. Lymphocyte-fibroblast adhesion. A useful model for analysis of the interaction of the leucocyte integrin LFA-1 with ICAM-1. FEBS Lett. 1991 Nov 4;292(1-2):284–288. doi: 10.1016/0014-5793(91)80885-7. [DOI] [PubMed] [Google Scholar]
  5. Carlos T. M., Harlan J. M. Leukocyte-endothelial adhesion molecules. Blood. 1994 Oct 1;84(7):2068–2101. [PubMed] [Google Scholar]
  6. Carlos T. M., Schwartz B. R., Kovach N. L., Yee E., Rosa M., Osborn L., Chi-Rosso G., Newman B., Lobb R., Rosso M. Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. Blood. 1990 Sep 1;76(5):965–970. [PubMed] [Google Scholar]
  7. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  8. Gao J. X., Issekutz A. C. Polymorphonuclear leucocyte migration through human dermal fibroblast monolayers is dependent on both beta 2-integrin (CD11/CD18) and beta 1-integrin (CD29) mechanisms. Immunology. 1995 Jul;85(3):485–494. [PMC free article] [PubMed] [Google Scholar]
  9. Haynes B. F., Hale L. P., Denning S. M., Le P. T., Singer K. H. The role of leukocyte adhesion molecules in cellular interactions: implications for the pathogenesis of inflammatory synovitis. Springer Semin Immunopathol. 1989;11(2):163–185. doi: 10.1007/BF00197187. [DOI] [PubMed] [Google Scholar]
  10. Lobb R. R., Hemler M. E. The pathophysiologic role of alpha 4 integrins in vivo. J Clin Invest. 1994 Nov;94(5):1722–1728. doi: 10.1172/JCI117519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lundgren-Akerlund E., Olofsson A. M., Berger E., Arfors K. E. CD11b/CD18-dependent polymorphonuclear leucocyte interaction with matrix proteins in adhesion and migration. Scand J Immunol. 1993 May;37(5):569–574. doi: 10.1111/j.1365-3083.1993.tb02573.x. [DOI] [PubMed] [Google Scholar]
  12. Makgoba M. W., Sanders M. E., Ginther Luce G. E., Dustin M. L., Springer T. A., Clark E. A., Mannoni P., Shaw S. ICAM-1 a ligand for LFA-1-dependent adhesion of B, T and myeloid cells. Nature. 1988 Jan 7;331(6151):86–88. doi: 10.1038/331086a0. [DOI] [PubMed] [Google Scholar]
  13. Marlor C. W., Webb D. L., Bombara M. P., Greve J. M., Blue M. L. Expression of vascular cell adhesion molecule-1 in fibroblastlike synoviocytes after stimulation with tumor necrosis factor. Am J Pathol. 1992 May;140(5):1055–1060. [PMC free article] [PubMed] [Google Scholar]
  14. Meng H., Marchese M. J., Garlick J. A., Jelaska A., Korn J. H., Gailit J., Clark R. A., Gruber B. L. Mast cells induce T-cell adhesion to human fibroblasts by regulating intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. J Invest Dermatol. 1995 Dec;105(6):789–796. doi: 10.1111/1523-1747.ep12326075. [DOI] [PubMed] [Google Scholar]
  15. Mobley J. L., Ennis E., Shimizu Y. Differential activation-dependent regulation of integrin function in cultured human T-leukemic cell lines. Blood. 1994 Feb 15;83(4):1039–1050. [PubMed] [Google Scholar]
  16. Morales-Ducret J., Wayner E., Elices M. J., Alvaro-Gracia J. M., Zvaifler N. J., Firestein G. S. Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes. J Immunol. 1992 Aug 15;149(4):1424–1431. [PubMed] [Google Scholar]
  17. Morzycki W., Issekutz A. C. Tumour necrosis factor-alpha but not interleukin-1 induces polymorphonuclear leucocyte migration through fibroblast layers by a fibroblast-dependent mechanism. Immunology. 1991 Sep;74(1):107–113. [PMC free article] [PubMed] [Google Scholar]
  18. Murakami S., Saho T., Shimabukuro Y., Isoda R., Miki Y., Okada H. Very late antigen integrins are involved in the adhesive interaction of lymphoid cells to human gingival fibroblasts. Immunology. 1993 Jul;79(3):425–433. [PMC free article] [PubMed] [Google Scholar]
  19. Norris P., Poston R. N., Thomas D. S., Thornhill M., Hawk J., Haskard D. O. The expression of endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in experimental cutaneous inflammation: a comparison of ultraviolet B erythema and delayed hypersensitivity. J Invest Dermatol. 1991 May;96(5):763–770. doi: 10.1111/1523-1747.ep12471720. [DOI] [PubMed] [Google Scholar]
  20. Osborn L., Hession C., Tizard R., Vassallo C., Luhowskyj S., Chi-Rosso G., Lobb R. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989 Dec 22;59(6):1203–1211. doi: 10.1016/0092-8674(89)90775-7. [DOI] [PubMed] [Google Scholar]
  21. Osborn L., Vassallo C., Benjamin C. D. Activated endothelium binds lymphocytes through a novel binding site in the alternately spliced domain of vascular cell adhesion molecule-1. J Exp Med. 1992 Jul 1;176(1):99–107. doi: 10.1084/jem.176.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Osborn L., Vassallo C., Browning B. G., Tizard R., Haskard D. O., Benjamin C. D., Dougas I., Kirchhausen T. Arrangement of domains, and amino acid residues required for binding of vascular cell adhesion molecule-1 to its counter-receptor VLA-4 (alpha 4 beta 1). J Cell Biol. 1994 Feb;124(4):601–608. doi: 10.1083/jcb.124.4.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pulido R., Elices M. J., Campanero M. R., Osborn L., Schiffer S., García-Pardo A., Lobb R., Hemler M. E., Sánchez-Madrid F. Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4. Correlation with distinct alpha 4 epitopes. J Biol Chem. 1991 Jun 5;266(16):10241–10245. [PubMed] [Google Scholar]
  24. Rothlein R., Czajkowski M., Kishimoto T. K. Intercellular adhesion molecule-1 in the inflammatory response. Chem Immunol. 1991;50:135–142. [PubMed] [Google Scholar]
  25. Sanchez-Madrid F., Nagy J. A., Robbins E., Simon P., Springer T. A. A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med. 1983 Dec 1;158(6):1785–1803. doi: 10.1084/jem.158.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schwachula A., Riemann D., Kehlen A., Langner J. Characterization of the immunophenotype and functional properties of fibroblast-like synoviocytes in comparison to skin fibroblasts and umbilical vein endothelial cells. Immunobiology. 1994 Feb;190(1-2):67–92. doi: 10.1016/S0171-2985(11)80284-6. [DOI] [PubMed] [Google Scholar]
  27. Seron D., Cameron J. S., Haskard D. O. Expression of VCAM-1 in the normal and diseased kidney. Nephrol Dial Transplant. 1991;6(12):917–922. doi: 10.1093/ndt/6.12.917. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Suchard S. J. Interaction of human neutrophils and HL-60 cells with the extracellular matrix. Blood Cells. 1993;19(2):197-221, discussion 221-3. [PubMed] [Google Scholar]
  30. Tang J., Scott G., Ryan D. H. Subpopulations of bone marrow fibroblasts support VLA-4-mediated migration of B-cell precursors. Blood. 1993 Dec 1;82(11):3415–3423. [PubMed] [Google Scholar]
  31. Vonderheide R. H., Springer T. A. Lymphocyte adhesion through very late antigen 4: evidence for a novel binding site in the alternatively spliced domain of vascular cell adhesion molecule 1 and an additional alpha 4 integrin counter-receptor on stimulated endothelium. J Exp Med. 1992 Jun 1;175(6):1433–1442. doi: 10.1084/jem.175.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vonderheide R. H., Tedder T. F., Springer T. A., Staunton D. E. Residues within a conserved amino acid motif of domains 1 and 4 of VCAM-1 are required for binding to VLA-4. J Cell Biol. 1994 Apr;125(1):215–222. doi: 10.1083/jcb.125.1.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wilkins J., Lyttle D., Sivananthan K., el-Gabalawy H. Lymphocyte-synovial cell interactions: a role for beta 1 and beta 3 integrin-mediated adhesion to cellular fibronectin. Cell Immunol. 1993 Feb;146(2):313–323. doi: 10.1006/cimm.1993.1029. [DOI] [PubMed] [Google Scholar]
  34. Wilkinson L. S., Edwards J. C., Poston R. N., Haskard D. O. Expression of vascular cell adhesion molecule-1 in normal and inflamed synovium. Lab Invest. 1993 Jan;68(1):82–88. [PubMed] [Google Scholar]
  35. Yang J., Xu Y., Zhu C., Hagan M. K., Lawley T., Offermann M. K. Regulation of adhesion molecule expression in Kaposi's sarcoma cells. J Immunol. 1994 Jan 1;152(1):361–373. [PubMed] [Google Scholar]
  36. van Dinther-Janssen A. C., Horst E., Koopman G., Newmann W., Scheper R. J., Meijer C. J., Pals S. T. The VLA-4/VCAM-1 pathway is involved in lymphocyte adhesion to endothelium in rheumatoid synovium. J Immunol. 1991 Dec 15;147(12):4207–4210. [PubMed] [Google Scholar]

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