Mechanisms of tobacco smoke toxicity on pulmonary macrophage cells

The enhanced morbidity from nonspecific respiratory infections found in smokers may be attributable to chemically-induced defects in the respiratory tract defense mechanisms that are organized around the alveolar macrophage. We have isolated by filtration and gas chromatography several cytotoxic components and single chemicals of the vapor phase of tobacco smoke and studied their cytotoxic effects on pulmonary alveolar macrophages. The filtered gas phase of cigarette smoke or acrolein suppresses phagocytic uptake and intracellular digestion of staphylococci when exposed in vitro; produces marked morphologic changes in the cytoplasmic membrane; inhibits cellular adhesion; disturbs glycolysis and arachidonic metabolism; inhibits calcium and magnesium ATPase, glyceraldehyde 3-phosphate dehydrogenase, and probably endoperoxide E-isomerase, but not sodium and potassium ATPase, glucose 6-phosphate dehydrogenase or lactic dehydrogenase in a dose-response fashion. Furthermore, in vivo studies show that acrolein exposure suppresses antibacterial defenses of the lung. These cellular deficiencies may be responsible for a significant component of altered host resistance in smokers who suffer increased morbidity from nonspecific respiratory infections.