Nicotine inhibits alpha-1-proteinase inhibitor inactivation by oxidants derived from human polymorphonuclear leukocytes.
Cigarette smoke can inactivate the alpha-1-proteinase inhibitor (alpha 1PI) by oxidative mechanisms and thus predisposes to the development of pulmonary emphysema. There are differences between the whole smoke and gas phase acting as alpha 1PI inactivators in vitro which suggests that the whole smoke is less oxidizing than the gas phase. Also studies on alpha 1PI 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 mumol/l to 4 mmol/l) on the oxidative inactivation of human alpha 1PI by phorbol myristate acetate-activated polymorphonuclear leukocytes (PMNL), chloramine-T (15 mumol/l), hydrogen peroxide (15 mmol/l) and the superoxide radical (O2-.) generating system-xanthine (0.2 mmol/l)-xanthine oxidase (80 U/l). Nicotine at concentrations of greater than 40 mumol/l protected alpha 1PI from stimulated PMNL. The preincubation of PMNL with these concentrations of nicotine did not diminish their ability to inactivate alpha 1PI after stimulation. Nicotine (above 0.4 mumol/l) also protected alpha 1PI from chloramine-T but not from H2O2. The inhibition of O2-.-mediated alpha 1PI inactivation by nicotine was low and was observed only at a concentration of 4 mmol/l. 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.
Nowak
D
D
Department of Pneumonology and Allergology, Institute of Internal Medicine, Medical Academy, Lódź, Poland.
Ruta
U
U
D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D010947:Plants, Toxic; D012906:Smoke / Q000009:adverse effects; D013481:Superoxides / Q000378:metabolism; D014026:Nicotiana; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D012906:Smoke; D000515:alpha 1-Antitrypsin; D013481:Superoxides; D009538:Nicotine; D006861:Hydrogen Peroxide