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

Abstract

SummaryAsthma 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 extraceUular 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 ot (TNF-ct). Activated, but not resting T cells, adhere to cultured ASM; stimulation of the ASM with TNF-a 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.

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

“…SP600125 also reduced eosinophil and CD 2 þ T-cell and eosinophil numbers and decreased ASM and epithelial cell proliferation. This does not establish a causative link between eosinophils and T cells, and airway smooth muscle hypertrophy, but direct interaction of activated CD4 þ T cells with airway smooth muscle cells can cause airway smooth muscle hyperplasia (Lazaar et al, 1994).…”

Allergen-Specific Th1 Cells Counteract Efferent Th2 Cell-Dependent Bronchial Hyperresponsiveness and Eosinophilic Inflammation Partly Via IFN-γ

“…It has been hypothesized that the activated eosinophils damage airways through cytotoxic mechanisms, thereby removing normal protective mechanisms and producing BHR (48,49). Alternatively, eosinophils may not always be required for BHR (50,51) and perhaps Th2 cells and cytokines may effect changes on airway smooth muscle cells directly (52). In our experiments, the fact that the added allergen-stimulated Th1 cells simultaneously suppressed BHR, IL-4 expression, and BAL eosinophilia is consistent with an action of Th1 cells on the Th2 asthma effector cascade formulated above.…”

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

“…In vivo studies in a Brown-Norway rat model show that sulphidopeptide leukotrienes and ET-1 are both involved in allergen-induced increases in airway smooth muscle proliferation [9,53,54]. Finally, activated T-cells can adhere to airway smooth muscle and induce its proliferation [12].…”

“…There is increased expression of a1 and a2 integrins, very late activation antigen (VLA)-4 and lymphocyte function associated receptor (LFA)-1, in bronchial biopsies of patients with asthma [62± 64]. Airway smooth muscle cells express intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 at barely detectable levels, but upregulate these adhesion molecules after treatment with TNFa for 24 h. Lipopolysaccharide, IL-1 and IFN also increased ICAM-1 expression, while VCAM-1 expression was increased by TNF and IL-1 [12]. Activation of T-cells is required for adhesion to airway smooth muscle cells.…”

“…However, in some animal models, increased proliferation of the airway smooth muscle following repeated allergen exposures after sensitization occurs [9±11]. In addition to the direct interaction of growth factors on the airway smooth muscle, the possibility that inflammatory cells, such as T-cells, could interact directly with the airway smooth muscle to induce proliferation has been raised [12]. Removal of serum factors that induce proliferation of airway smooth muscle in vitro following confluence results in a population of elongated cells with an ability to shorten considerably [13], together with an increase in smooth muscle a-actin and myosin heavy chain [14].…”