CIGARETTE-SMOKE EXTRACT INHIBITS FIBROBLAST-MEDIATED COLLAGEN GEL CONTRACTION

Cigarette smoking, the major cause of pulmonary emphysema, is characte rized by destruction of alveolar walls. Because tissue destruction rep resents a balance between injury and repair, we hypothesized that ciga rette smoke exposure may contribute to the development of emphysema th rough the inhibition of tissue contraction during the repair process. To partially evaluate this hypothesis, we investigated the effects of cigarette smoke extract (CSE) on the ability of cultured fibroblasts t o mediate collagen gel contraction in vitro: CSE inhibited fibroblast- mediated gel contraction in a concentration-dependent manner (P < 0.01 ). Production of prostaglandin E-2, a known inhibitor of fibroblast co ntraction, was unchanged by CSE as was cell surface integrin expressio n. In contrast, fibronectin production by fibroblasts was inhibited (P < 0.01), and addition of exogenous fibronectin partially restored the contractile activity, thus suggesting at least one mechanism to expla in inhibition of gel contraction by CSE. When CSE was treated to remov e volatile components, it showed less inhibitory activity on fibroblas t-mediated gel contraction. Therefore, we also examined the effects of acrolein and acetaldehyde, two volatile components of cigarette smoke . Inhibition of contraction was observed at 5 mu M acrolein and at 0.5 mM acetaldehyde. In conclusion, cigarette smoke inhibited fibroblast- mediated gel contraction, and this inhibition was due, at least in par t, to the volatile components of cigarette smoke and may be mediated, at least in part, by a decrease in fibroblast fibronectin production. By inhibition of repair, these smoke components may contribute to the development of pulmonary emphysema.