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. 1994 Sep 1;180(3):807–816. doi: 10.1084/jem.180.3.807

T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis

PMCID: PMC2191657  PMID: 7520473

Abstract

Asthma is a disease of airway inflammation and hyperreactivity that is associated with a lymphocytic infiltrate in the bronchial submucosa. The interactions between infiltrating T lymphocytes with cellular and extracellular matrix components of the airway and the consequences of these interactions have not been defined. We demonstrate the constitutive expression of CD44 on human airway smooth muscle (ASM) cells in culture as well as in human bronchial tissue transplanted into severe combined immunodeficient mice. In contrast, basal levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression are minimal but are induced on ASM by inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha). Activated, but not resting T cells, adhere to cultured ASM; stimulation of the ASM with TNF-alpha enhanced this adhesion. Adhesion was partially blocked by monoclonal antibodies (mAb) specific for lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) on T cells and ICAM-1 and VCAM-1 on ASM cells. The observed integrin-independent adhesion was mediated by CD44/hyaluronate interactions as it was inhibited by anti-CD44 mAb 5F12 and by hyaluronidase. Furthermore, the adhesion of activated T lymphocytes induced DNA synthesis in growth-arrested ASM cells. Thus, the interaction between T cells and ASM may provide insight into the mechanisms that induce bronchial inflammation and possibly ASM cell hyperplasia seen in asthma.

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Selected References

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  1. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  2. Broide D. H., Lotz M., Cuomo A. J., Coburn D. A., Federman E. C., Wasserman S. I. Cytokines in symptomatic asthma airways. J Allergy Clin Immunol. 1992 May;89(5):958–967. doi: 10.1016/0091-6749(92)90218-q. [DOI] [PubMed] [Google Scholar]
  3. Bruynzeel I., Koopman G., van der Raaij L. M., Pals S. T., Willemze R. CD44 antibody stimulates adhesion of peripheral blood T cells to keratinocytes through the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway. J Invest Dermatol. 1993 Apr;100(4):424–428. doi: 10.1111/1523-1747.ep12472106. [DOI] [PubMed] [Google Scholar]
  4. Camp R. L., Scheynius A., Johansson C., Puré E. CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation. J Exp Med. 1993 Aug 1;178(2):497–507. doi: 10.1084/jem.178.2.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Couffinhal T., Duplàa C., Labat L., Lamaziere J. M., Moreau C., Printseva O., Bonnet J. Tumor necrosis factor-alpha stimulates ICAM-1 expression in human vascular smooth muscle cells. Arterioscler Thromb. 1993 Mar;13(3):407–414. doi: 10.1161/01.atv.13.3.407. [DOI] [PubMed] [Google Scholar]
  7. DeLisser H. M., Chilkotowsky J., Yan H. C., Daise M. L., Buck C. A., Albelda S. M. Deletions in the cytoplasmic domain of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) result in changes in ligand binding properties. J Cell Biol. 1994 Jan;124(1-2):195–203. doi: 10.1083/jcb.124.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Djukanović R., Roche W. R., Wilson J. W., Beasley C. R., Twentyman O. P., Howarth R. H., Holgate S. T. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434–457. doi: 10.1164/ajrccm/142.2.434. [DOI] [PubMed] [Google Scholar]
  9. Dunnill M. S., Massarella G. R., Anderson J. A. A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis, and in emphysema. Thorax. 1969 Mar;24(2):176–179. doi: 10.1136/thx.24.2.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dustin M. L., Springer T. A. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature. 1989 Oct 19;341(6243):619–624. doi: 10.1038/341619a0. [DOI] [PubMed] [Google Scholar]
  11. Gerblich A. A., Salik H., Schuyler M. R. Dynamic T-cell changes in peripheral blood and bronchoalveolar lavage after antigen bronchoprovocation in asthmatics. Am Rev Respir Dis. 1991 Mar;143(3):533–537. doi: 10.1164/ajrccm/143.3.533. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Gonchoroff N. J., Greipp P. R., Kyle R. A., Katzmann J. A. A monoclonal antibody reactive with 5-bromo-2-deoxyuridine that does not require DNA denaturation. Cytometry. 1985 Nov;6(6):506–512. doi: 10.1002/cyto.990060604. [DOI] [PubMed] [Google Scholar]
  14. Gosset P., Tsicopoulos A., Wallaert B., Vannimenus C., Joseph M., Tonnel A. B., Capron A. Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. J Allergy Clin Immunol. 1991 Oct;88(4):561–571. doi: 10.1016/0091-6749(91)90149-i. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Johnston S. C., Dustin M. L., Hibbs M. L., Springer T. A. On the species specificity of the interaction of LFA-1 with intercellular adhesion molecules. J Immunol. 1990 Aug 15;145(4):1181–1187. [PubMed] [Google Scholar]
  17. 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]
  18. Leff A. R., Hamann K. J., Wegner C. D. Inflammation and cell-cell interactions in airway hyperresponsiveness. Am J Physiol. 1991 Apr;260(4 Pt 1):L189–L206. doi: 10.1152/ajplung.1991.260.4.L189. [DOI] [PubMed] [Google Scholar]
  19. Lesley J., He Q., Miyake K., Hamann A., Hyman R., Kincade P. W. Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody. J Exp Med. 1992 Jan 1;175(1):257–266. doi: 10.1084/jem.175.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lesley J., Hyman R. CD44 can be activated to function as an hyaluronic acid receptor in normal murine T cells. Eur J Immunol. 1992 Oct;22(10):2719–2723. doi: 10.1002/eji.1830221036. [DOI] [PubMed] [Google Scholar]
  21. Li H., Cybulsky M. I., Gimbrone M. A., Jr, Libby P. Inducible expression of vascular cell adhesion molecule-1 by vascular smooth muscle cells in vitro and within rabbit atheroma. Am J Pathol. 1993 Dec;143(6):1551–1559. [PMC free article] [PubMed] [Google Scholar]
  22. Liao H. X., Levesque M. C., Patton K., Bergamo B., Jones D., Moody M. A., Telen M. J., Haynes B. F. Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies. J Immunol. 1993 Dec 1;151(11):6490–6499. [PubMed] [Google Scholar]
  23. Metzger W. J., Zavala D., Richerson H. B., Moseley P., Iwamota P., Monick M., Sjoerdsma K., Hunninghake G. W. Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Description of the model and local airway inflammation. Am Rev Respir Dis. 1987 Feb;135(2):433–440. doi: 10.1164/arrd.1987.135.2.433. [DOI] [PubMed] [Google Scholar]
  24. Miyake K., Medina K. L., Hayashi S., Ono S., Hamaoka T., Kincade P. W. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. J Exp Med. 1990 Feb 1;171(2):477–488. doi: 10.1084/jem.171.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Montefort S., Roche W. R., Howarth P. H., Djukanovic R., Gratziou C., Carroll M., Smith L., Britten K. M., Haskard D., Lee T. H. Intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects. Eur Respir J. 1992 Jul;5(7):815–823. [PubMed] [Google Scholar]
  26. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  27. Oppenheimer-Marks N., Davis L. S., Bogue D. T., Ramberg J., Lipsky P. E. Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T lymphocytes. J Immunol. 1991 Nov 1;147(9):2913–2921. [PubMed] [Google Scholar]
  28. Panettieri R. A., Murray R. K., DePalo L. R., Yadvish P. A., Kotlikoff M. I. A human airway smooth muscle cell line that retains physiological responsiveness. Am J Physiol. 1989 Feb;256(2 Pt 1):C329–C335. doi: 10.1152/ajpcell.1989.256.2.C329. [DOI] [PubMed] [Google Scholar]
  29. Panettieri R. A., Yadvish P. A., Kelly A. M., Rubinstein N. A., Kotlikoff M. I. Histamine stimulates proliferation of airway smooth muscle and induces c-fos expression. Am J Physiol. 1990 Dec;259(6 Pt 1):L365–L371. doi: 10.1152/ajplung.1990.259.6.L365. [DOI] [PubMed] [Google Scholar]
  30. Robinson D. S., Hamid Q., Ying S., Tsicopoulos A., Barkans J., Bentley A. M., Corrigan C., Durham S. R., Kay A. B. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992 Jan 30;326(5):298–304. doi: 10.1056/NEJM199201303260504. [DOI] [PubMed] [Google Scholar]
  31. Rothlein R., Czajkowski M., O'Neill M. M., Marlin S. D., Mainolfi E., Merluzzi V. J. Induction of intercellular adhesion molecule 1 on primary and continuous cell lines by pro-inflammatory cytokines. Regulation by pharmacologic agents and neutralizing antibodies. J Immunol. 1988 Sep 1;141(5):1665–1669. [PubMed] [Google Scholar]
  32. Sanchez-Madrid F., Krensky A. M., Ware C. F., Robbins E., Strominger J. L., Burakoff S. J., Springer T. A. Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7489–7493. doi: 10.1073/pnas.79.23.7489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Shimizu Y., Newman W., Gopal T. V., Horgan K. J., Graber N., Beall L. D., van Seventer G. A., Shaw S. Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions. J Cell Biol. 1991 Jun;113(5):1203–1212. doi: 10.1083/jcb.113.5.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shimizu Y., Van Seventer G. A., Siraganian R., Wahl L., Shaw S. Dual role of the CD44 molecule in T cell adhesion and activation. J Immunol. 1989 Oct 15;143(8):2457–2463. [PubMed] [Google Scholar]
  35. Stemme S., Fager G., Hansson G. K. MHC class II antigen expression in human vascular smooth muscle cells is induced by interferon-gamma and modulated by tumour necrosis factor and lymphotoxin. Immunology. 1990 Feb;69(2):243–249. [PMC free article] [PubMed] [Google Scholar]
  36. Stemme S., Patarroyo M., Hansson G. K. Adhesion of activated T lymphocytes to vascular smooth muscle cells and dermal fibroblasts is mediated by beta 1- and beta 2-integrins. Scand J Immunol. 1992 Aug;36(2):233–242. doi: 10.1111/j.1365-3083.1992.tb03095.x. [DOI] [PubMed] [Google Scholar]
  37. Warner S. J., Friedman G. B., Libby P. Regulation of major histocompatibility gene expression in human vascular smooth muscle cells. Arteriosclerosis. 1989 May-Jun;9(3):279–288. doi: 10.1161/01.atv.9.3.279. [DOI] [PubMed] [Google Scholar]
  38. Wegner C. D., Gundel R. H., Reilly P., Haynes N., Letts L. G., Rothlein R. Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma. Science. 1990 Jan 26;247(4941):456–459. doi: 10.1126/science.1967851. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. van Kooyk Y., van de Wiel-van Kemenade E., Weder P., Huijbens R. J., Figdor C. G. Lymphocyte function-associated antigen 1 dominates very late antigen 4 in binding of activated T cells to endothelium. J Exp Med. 1993 Jan 1;177(1):185–190. doi: 10.1084/jem.177.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]

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