Stimuli-induced superoxide radical generation in vitro by human alveolar macrophages from smokers: Modulation by n-acetylcysteine treatment in vivo

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Abstract

Bronchoalveolar lavage (BAL) was performed on nine healthy nonsmoking subjects and on 11 healthy smokers; in the last mentioned group lavage was performed before and after eight weeks treatment with N-acetyl-cysteine (NAC; 200 mg t.i.d.). The BAL cells were cultured for 2 h or overnight. Adherent cells were examined for their capacity to generate Superoxide radicals (determined by Superoxide dismutase (SOD)-inhibitable cytochrome C-reduction) at stimulation with phorbol 12-myristate 13-acetate (PMA), serum-treated zymosan (STZ), the calcium ionophore A23187, or the chemotactic tripeptide formyl-methionylleucylphenylalanine (FMLP). Cells from nonsmokers responded with a very low degree of O2⨪-generation to any of the stimuli employed whether cultured for 2 h or overnight. Cells from smokers also responded with low O2⨪-generation after 2 h of culture. However, cells from smokers cultured overnight responded with marked O2⨪-generation to PMA and STZ but the responses to FMLP and A23187 were low. NAC-treatment of the smokers resulted in a reduced degree of both PMA- and STZ-induced O2⨪-generation in five individuals. In two other subjects, PMA-induced (but not STZ-induced) O2⨪-generation was reduced. Two individuals showed increased O2⨪-generation to PMA- and to STZ-stimulation after NAC-treatment. Mean values of O2⨪-generation induced by A23l87orby FMLP were significantly reduced for cells harvested after NAC-treatment. Mean values for PMA-induced O2⨪ -generation also tended to be reduced by the treatment. We conclude that smoking leads to an increased capacity of alveolar adherent cells to generate O2⨪ at appropriate stimulation and propose that treatment with NAC may reduce this capacity in a substantial number of the examined individuals.

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