Nicotine prolongs neutrophil survival by suppressing apoptosis.
Neutrophil accumulation in the lung is implicated in the pathogenesis of pulmonary emphysema and chronic bronchitis associated with cigarette smoking. To determine whether nicotine contributes to this accumulation through the prolongation of neutrophil survival, we examined the survival rates of isolated neutrophils cultured with or without nicotine. We found that nicotine prolonged neutrophil survival in a dose-dependent fashion, with a maximum effect at 10(-6) mol/L. The survival rate at 72 hours was 35.6% +/- 1.2% in medium with 10(-6) mol/L nicotine, compared with 15.5% +/- 0.5% in control medium (mean +/- SEM; p < 0.01), as determined by trypan blue dye exclusion. This prolongation was brought about by suppression of apoptosis, as evidenced by both transmission electron and fluorescence microscopy, and was associated with the preservation of neutrophil functions such as chemotaxis and O2- generation. The prolongation of survival caused by nicotine was abrogated by the addition of Pro-Lys-Arg-NH2, a competitive inhibitor of the specific binding of nicotine to noncholinergic receptors on neutrophils. However, the prolongation of survival caused by nicotine was not suppressed in the presence of K-252b, an inhibitor of protein kinase C. These findings suggest that nicotine prolongs neutrophil survival through noncholinergic nicotine receptors and new protein synthesis, without activation of protein kinase C.
Aoshiba
K
K
First Department of Medicine, Tokyo Women's Medical College, Japan.
Nagai
A
A
Yasui
S
S
Konno
K
K
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D004247:DNA / Q000097:blood / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids; D007700:Kinetics; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011978:Receptors, Nicotinic / Q000502:physiology; D012016:Reference Values; D012907:Smoking / Q000503:physiopathology; D013481:Superoxides / Q000097:blood; D013997:Time Factors; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
D002227:Carbazoles; D002843:Chromatin; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D018733:Nicotinic Antagonists; D009842:Oligopeptides; C099514:Pro-Lys-Arg-NH2; D011978:Receptors, Nicotinic; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009538:Nicotine; D004247:DNA; C049985:staurosporine aglycone; D011493:Protein Kinase C