Relation of cytosolic calcium to the microbicidal activation of blood monocytes by recombinant gamma interferon.
Oxygen metabolism and calcium ion (Ca++) handling in blood monocytes were greatly affected by treatment with recombinant gamma interferon (rIFN-gamma). Incubating the monocytes with rIFN-gamma resulted in increased basal production of superoxide anion, as well as a significantly enhanced respiratory burst in response to concanavalin A (Con A). A concomitant increase in microbicidal activity against Listeria monocytogenes was observed, and cell membrane permeability to Ca++ was enhanced by treatment with rIFN-gamma. Con A stimulation was also associated with acute rises in cytosolic-free calcium, and these calcium transients were greatly augmented in cells pretreated with rIFN-gamma. The enhanced respiratory burst and the increased calcium transients were completely neutralized by a monoclonal antibody to rIFN-gamma. Furthermore, enhancement of the respiratory burst and calcium transients occurred in a parallel dose-response range for rIFN-gamma. Blocking the intracellular release of calcium into cytosol by TMB-8 abrogated the capacity of rIFN-gamma to enhance the monocyte respiratory burst. Thus, not only was rIFN-gamma treatment of monocytes associated with altered calcium metabolism, but calcium from intracellular pools was essential to the expression of this activated state during Con A stimulation.
D001770:Blood Bactericidal Activity; D002118:Calcium / Q000032:analysis*; D002448:Cell Adhesion / Q000187:drug effects; D002463:Cell Membrane Permeability; D003208:Concanavalin A / Q000494:pharmacology; D003600:Cytosol / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology*; D013481:Superoxides / Q000096:biosynthesis
D011994:Recombinant Proteins; D003208:Concanavalin A; D013481:Superoxides; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D007371:Interferon-gamma; D010100:Oxygen; D002118:Calcium