Modulation of the inhibition of respiratory burst in mouse macrophages by cyclosporin A: effect of in vivo treatment, glucocorticoids and the state of activation of cells.
Cyclosporin A (CsA) is an immunosuppressor without myelotoxicity. It is thought that its effect is mediated by inhibition of Interleukin-2 (IL-2) receptor expression in lymphocytes. We have recently described that CsA reduces phorbol 12-myristate 13-acetate (PMA)-dependent superoxide anion and H2O2 production by resident mice macrophages in vitro. The present work provides evidence that the capacity of CsA to produce this inhibition is abolished when macrophages are in the activated state. We also show that peritoneal macrophages from CsA-treated mice retain the capacity to inhibit O2- production. The interaction between CsA and glucocorticoids in vitro shows a co-operative effect between both agents. These studies demonstrate a novel action of CsA related to its modulation of the inhibition of the respiratory burst. The physiological role of these CsA effects and modulation need further exploration.
Chiara
M D
MD
Departamento de Bioquimica Médica y Biologia Molecular, Facultad de Medicina, Universidad de Sevilla, Spain.
Sobrino
F
F
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D010101:Oxygen Consumption / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003524:Cyclosporins; D005938:Glucocorticoids; D013481:Superoxides; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium