Al. Lazaar et al., T-LYMPHOCYTES ADHERE TO AIRWAY SMOOTH-MUSCLE CELLS VIA INTEGRINS AND CD44 AND INDUCE SMOOTH-MUSCLE CELL-DNA SYNTHESIS, The Journal of experimental medicine, 180(3), 1994, pp. 807-816
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 constitut
ive expression of CD44 on human airway smooth muscle (ASM) cells in cu
lture as well as in human bronchial tissue transplanted into severe co
mbined immunodeficient mice. In contrast, basal levels of intercellula
r 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 AS
M with TNF-cr enhanced this adhesion. Adhesion was partially blocked b
y monoclonal antibodies (mAb) specific for lymphocyte function-associa
ted antigen 1 (LFA-1) and very late antigen 4 (VLA-4) on T cells and I
CAM-1 and VCAM-1 on ASM cells. The observed integrin-independent adhes
ion 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 AS
M cells. Thus, the interaction between T cells and ASM may provide ins
ight into the mechanisms that induce bronchial inflammation and possib
ly ASM cell hyperplasia seen in asthma.