Alterations of guinea pig alveolar macrophage oxidative metabolism by nicotine

The influence of nicotine, a cholinergic agonist, on guinea pig pulmonary alveolar macrophage (PAM) oxidative metabolism was examined. Nicotine caused a concentration-dependent enhancement or inhibition of chemiluminescence response and superoxide anion release by zymosan-stimulated PAM. Thus, at 5 x 10(-10) and 5 x 10(-8) M of nicotine the chemiluminescence response was augmented to 132 and 113%, respectively. At higher concentrations, such as 5 x 10(-7) and 1 x 10(-4) M, however, these responses were inhibited to 83 and 51% of the control, respectively. Similarly, at 5 x 10(-10) and 5 x 10(-9) M nicotine, superoxide anion release was enhanced to 226 and 209% of the control, respectively. Higher concentrations of nicotine, 5 x 10(-5) and 5 x 10(-4) M, inhibited this response to 53 and 58% of the control, respectively. Neither the potentiating nor the inhibitory effect of nicotine was affected by a muscarinic (atropine) or nicotinic (hexamethonium) cholinergic antagonist. None of the drugs examined, by themselves, stimulated PAM oxidative metabolism or influenced oxyradical generation by a cell-free system. This study demonstrates that nicotine, a major component of cigarette smoke, may play a significant role in the pathogenesis of some pulmonary diseases.