NICOTINE INHIBITS ALPHA-1-PROTEINASE INHIBITOR INACTIVATION BY OXIDANTS DERIVED FROM HUMAN POLYMORPHONUCLEAR LEUKOCYTES

Cigarette smoke can inactivate the α-1-proteinase inhibitor (α1PI) by oxidative mechanisms and thus predisposes to the development of pulmonary emphysema. There are differences between the whole smoke and gas phase acting as α1PI inactivators in vitro which suggests that the whole smoke is less oxidizing than the gas phase. Also studies on α1PI oxidative inactivation in the lung of cigarette smokers gave controversial results. The reductive properties of cigarette tar which contains most of smoke nicotine may be some explanation of it. Therefore in this study we have investigated the effect of nicotine (0.4 umol/1 to 4 mmol/1) on the oxidative inactivation of human α1PI by phorbol myristate acetate-activated polymorphonuclear leukocytes (PMNL), chloramine-T (15 (μmol/1), hydrogen peroxide (15 mmol/1) and the Superoxide radical (O2-) generating system-xanthine (0.2 mmol/l)-xanthine oxidase (80 U/1). Nicotine at concentrations of >40 μmol/1 protected α1PI from stimulated PMNL. The preincubation of PMNL with these concentrations of nicotine did not diminish their ability to inactivate α1PI after stimulation. Nicotine (above 0.4 μmol/1) also protected α1PI from chloramine-T but not from H2O2. The inhibition of O2--mediated α1PI inactivation by nicotine was low and was observed only at a concentration of 4 mmol/1. This nicotine concentration did not affect xanthine oxidase activity. It is suggested that cigarettes with low nicotine contents can cause greater oxidative lung injury than their high nicotine counterparts and be a greater risk factor for the development of lung emphysema. © 1990, VEB Gustav Fischer Verlag Jena. All rights reserved.