Amiloride does not influence the capability of interferon gamma to potentiate superoxide anion and hydrogen peroxide release by human mononuclear phagocytes.
Since the molecular mechanisms of macrophage activation in response to interferon gamma (IFN-gamma) are still not well defined we have investigated whether amiloride, a specific inhibitor of the Na+/H+ antiporter, had any effect on the IFN-gamma-mediated potentiation of human monocyte and monocyte-derived macrophage capability to produce O2- (respiratory burst). Here, we demonstrate that amiloride neither inhibits the capability of IFN-gamma to activate the mononuclear phagocyte respiratory burst nor influences IFN-gamma induction of steady-state mRNA levels for 2 components of the superoxide anion-generating enzyme system. On the contrary, we show that IFN-gamma-enhanced expression of the HLA-DR alpha gene is significantly inhibited by amiloride These data indicate that Na+/H+ antiporter stimulation by IFN-gamma is not involved in the mechanism of activation of macrophage oxidative metabolism.
Cassatella
M A
MA
Institute of General Pathology, University of Verona, Italy.
Peroni
D
D
Amezaga
M A
MA
Vicentini
F
F
Bazzoni
F
F
D000584:Amiloride / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers; D013481:Superoxides / Q000378:metabolism*
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D013481:Superoxides; D000584:Amiloride; D007371:Interferon-gamma; D006861:Hydrogen Peroxide