Cyclosporin A inhibits phorbol ester-induced activation of superoxide production in resident mouse peritoneal macrophages.
Peritoneal resident macrophages from mice are sensitive to inhibition by cyclosporin A (CsA) of phorbol 12-myristate 13-acetate (PMA)-stimulated oxidative burst. Inhibition was assessed in terms of superoxide anion (O2.-) and H2O2 production. Key findings were as follows. (a) CsA inhibited in a dose-dependent manner the production of O2.- when cells were stimulated with PMA. CsA did not alter the respiratory burst induced by other stimuli (zymosan, concanavalin A and fMet-Leu-Phe). It was verified that CsA itself had no scavenger effect. (b) A concomitant decrease in H2O2 liberation following CsA exposure was found. This inhibition was observed both in the initial rate of synthesis and in the accumulation after 15 min of incubation. (c) NADPH oxidase activity in the crude supernatant was unaffected by the previous incubation of macrophages with CsA. CsA does not inhibit glucose transport measured as 14CO2 production. (d) The production of O2.- was strongly dependent on the glucose concentration. Sodium oleate also stimulated O2.- production in resident macrophages. These data might be correlated with the inhibitory effect of CsA upon other functions of macrophages.
Chiara
M D
MD
Departamento de Bioquímica Medica y Biología Molecular, Facultad de Medicina, Universidad de Sevilla, Spain.
Bedoya
F
F
Sobrino
F
F
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009249:NADP / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003524:Cyclosporins; D009829:Oleic Acids; D013481:Superoxides; D019301:Oleic Acid; D009249:NADP; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate