Superoxide formed from cigarette smoke impairs polymorphonuclear leukocyte active oxygen generation activity.
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.
Tsuchiya
M
M
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Thompson
D F
DF
Suzuki
Y J
YJ
Cross
C E
CE
Packer
L
L
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
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