Cytotoxic effects of cigarette smoke extract on an alveolar type II cell-derived cell line

Injury of the alveolar epithelium by cigarette smoke is presumed to be an i mportant process in the pathogenesis of smoking-related pulmonary diseases. We investigated the cytotoxic effects of cigarette smoke extract (CSE) on an alveolar type II cell-derived cell line (A549). CSE caused apoptosis at concentrations of 5% or less and necrosis at 10% or more. When CSE was expo sed to air before application to A549 cells, the cytotoxic effects were att enuated. CSE caused cell death without direct contact with the cells. Acrol ein and hydrogen peroxide, two major volatile factors in cigarette smoke, c aused cell death in a similar manner. Aldehyde dehydrogenase, a scavenger o f aldehydes, and N-acetylcysteine, a scavenger of oxidants and aldehydes, c ompletely inhibited CSE-induced apoptosis. CSE and acrolein increased intra cellular oxidant activity. In conclusion, apoptosis of alveolar epithelial cells may be one of the mechanisms of lung injury induced by cigarette smok ing. This cytotoxic effect might be due to an interaction between aldehydes and oxidants present in CSE or formed in CSE-exposed cells.