Pharmacoprevention of tobacco smoke effects on macrophage cells

Cigarette smoke components produce a variety of morphologic, physiologic, biochemical, and enzymatic changes in pulmonary alveolar macrophages, cells which are important in pulmonary antibacterial defenses, cellular regulatory activity, and tissue pathogenesis of inflammation, proteolysis and fibrogenesis. A common denominator of enzymes found to be inhibited by cigarette smoke components is a sulfhydryl moiety which is critical to the functioning of the enzyme and highly susceptible to oxidant activity of substances with the properties of agents in cigarette smoke. The inhibitory effect of cigarette smoke components on glyceraldehyde 3-phosphate dehydrogenase, calcium and magnesium ATPase, and endoperoxide E-isomerase is quantitatively prevented by the addition of sulfhydryl agents such as glutathione and cysteine. Furthermore, critical functions of whole cell activity such as phagocytosis, energy metabolism, and prostaglandin synthesis and release, functions which are dependent on sulfhydryl enzymes and are inhibited by cigarette smoke components, are protected when glutathione or cysteine are provided in advance of the exposure. These sulfhydryl agents also protect adhesion and cellular morphology from derangement by cigarette smoke components. These in vitro studies suggest a role for sulfhydryl-containing agents in the prevention of environmentally-induced injuries to alveolar macrophages.