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.
Article|
September 01 1994
T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis.
A L Lazaar,
A L Lazaar
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
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S M Albelda,
S M Albelda
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
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J M Pilewski,
J M Pilewski
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
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B Brennan,
B Brennan
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
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E Puré,
E Puré
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
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R A Panettieri, Jr
R A Panettieri, Jr
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
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A L Lazaar
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
S M Albelda
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
J M Pilewski
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
B Brennan
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
E Puré
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
R A Panettieri, Jr
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1994) 180 (3): 807–816.
Citation
A L Lazaar, S M Albelda, J M Pilewski, B Brennan, E Puré, R A Panettieri; T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis.. J Exp Med 1 September 1994; 180 (3): 807–816. doi: https://doi.org/10.1084/jem.180.3.807
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