Evidence for generation of a large amount of nitric oxide-like vascular smooth muscle relaxant by cholesterol-rich neutrophils.
To determine the effect of cholesterol incorporation on the ability of neutrophils to generate superoxide radicals and nitric oxide-like vasorelaxant material, isolated human neutrophils were incubated with cholesterol-rich liposomes, which increased total cholesterol content by 141% and esterified cholesterol content by 523%. Cholesterol loading resulted in 5 to 7 fold increase in cytosolic calcium in resting as well as in PMA or f-MLP-stimulated cells, but a marked (P less than 0.01) reduction in both PMA- and f-MLP-stimulated superoxide radical generation by these cells. Nitric oxide-like activity measured as relaxation of rat aortic rings was more pronounced (P less than 0.02) in cholesterol-rich than in cholesterol-poor cells. The greater relaxation of aortic rings in response to cholesterol-rich neutrophils was observed in rings with or without intact endothelium, and was potentiated by superoxide dismutase and inhibited by oxyhemoglobin as well as L-NMMA, thus suggesting that the vasorelaxant material was nitric oxide. The greater generation of nitric oxide by cholesterol-rich neutrophils occurs perhaps in response to increased cytosolic calcium.
Mehta
J L
JL
Department of Medicine, University of Florida College of Medicine, Gainesville.
Lawson
D L
DL
Nicolini
F A
FA
Cain
D A
DA
Mehta
P
P
Schreier
H
H
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008081:Liposomes; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood* / Q000494:pharmacology; D019335:Nitroarginine; D010108:Oxyhemoglobins / Q000494:pharmacology; D051381:Rats; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019323:omega-N-Methylarginine
D008081:Liposomes; D010108:Oxyhemoglobins; D013481:Superoxides; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D001120:Arginine; D002784:Cholesterol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D007213:Indomethacin