Nicotine potentiates superoxide anion generation by human neutrophils.

Cytotoxic neutrophil-derived oxygen radicals have been implicated in the pathogenesis of a variety of cardiovascular, pulmonary, and neoplastic disorders for which cigarette smoking is a prominent risk factor. Although nicotine alone failed to provoke neutrophil oxidative metabolism, the alkaloid caused dose-dependent (0.1 to 10 microM) potentiation of superoxide anion release induced by either phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine. The potentiating effect of nicotine was not attenuated by either atropine or hexamethonium nor was it mimicked by acetylcholine, suggesting involvement of noncholinergic receptors or a membrane-fluidizing effect of the alkaloid. Nicotine-induced exacerbation of neutrophil superoxide anion production may be involved with the enhanced risk of cardiovascular, pulmonary, or neoplastic disease in individuals who smoke.