title: Superoxide formed from cigarette smoke impairs polymorphonuclear leukocyte active oxygen generation activity.
abstract: Reactive free radicals contained in cigarette smoke (CS) and compromised phagocytic antimicrobial activities including those of polymorphonuclear leukocytes (PMNs) have been implicated in the pathogenesis of severe CS-related pulmonary disorders. In CS-exposed buffer solutions, O2-. was the predominant generated reactive oxygen species, as demonstrated by lucigenin-amplified chemiluminescence and electron spin resonance (ESR) spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). When PMNs were incubated in this buffer, phorbol 12-myristate 13-acetate (PMA)-stimulated active oxygen production and coupled O2 consumption were strongly impaired without appreciably affecting PMN viability (1-min exposure inhibited active oxygen production by 75%). Superoxide dismutase (SOD) totally protected and an iron chelator, diethylenetriaminepentaacetic acid (DETAPAC), also protected the CS-exposed PMNs, suggesting that generated O2-. was an initiating factor in the impairment and OH. generation was a subsequent injurious factor. Pretreatment of PMNs with antioxidants such as alpha-tocopherol and dihydrolipoic acid (DHLA) was partially protective. The results suggest that (i) O2-. is probably generated in the upper and lower respiratory tract lining fluid when they come in contact with CS; (ii) such generated O2-. can primarily impair PMN capabilities to generate reactive oxygen species; and (iii) since these effects may contribute to the pathogenesis of CS-related lung diseases, prior supplementation with antioxidants such as alpha-tocopherol or DHLA might be successful in preventing these deleterious effects.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley 94720.
authors.forename: M
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: D F
authors.initials: DF
authors.lastname: Thompson
authors.forename: Y J
authors.initials: YJ
authors.lastname: Suzuki
authors.forename: C E
authors.initials: CE
authors.lastname: Cross
authors.forename: L
authors.initials: L
authors.lastname: Packer
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D008163:Luminescent Measurements; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010947:Plants, Toxic; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D008063:Thioctic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D014026:Nicotiana; D014810:Vitamin E / Q000494:pharmacology; D019207:beta Carotene
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D012906:Smoke; D013113:Spin Labels; D019207:beta Carotene; D013481:Superoxides; D014810:Vitamin E; D002338:Carotenoids; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D013755:Tetradecanoylphorbol Acetate