T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis.
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.
Lazaar
A L
AL
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia.
Albelda
S M
SM
Pilewski
J M
JM
Brennan
B
B
Puré
E
E
Panettieri
R A
RA
D000818:Animals; D001980:Bronchi / Q000166:cytology* / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis; D002450:Cell Communication; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D006801:Humans; D018960:Hyaluronan Receptors; D016023:Integrins / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1; D051379:Mice; D016513:Mice, SCID; D009130:Muscle, Smooth / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D014132:Trachea / Q000166:cytology* / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D016023:Integrins; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004247:DNA