Molecular basis for the enhanced respiratory burst of activated macrophages.
Macrophages elicited by injection of agents that produce inflammation or obtained from animals infected with intracellular parasites are primed so that they respond to phagocytosis or exposure to phorbol myristate acetate with a marked increase in the respiratory burst. This capacity to respond to stimulation with increased release of reactive oxygen metabolites appears to play an essential role in the increased microbicidal capability of activated macrophages. Macrophages can be primed for this capacity by incubation in vitro with bacterial products, proteases, or gamma interferon. The molecular basis for this priming is presently under investigation. An increase in the number or affinity of plasma membrane receptors does not appear to explain priming. Changes in one or more of the transduction events responsible for stimulus-response coupling might lead to more efficient stimulation or function of the enzyme responsible for the respiratory burst; these events are just beginning to be studied in macrophages. Priming can be explained at least in part by a modification of the respiratory burst enzyme such that it binds its substrate NADPH, the source of electrons for reduction of oxygen to superoxide anion, more efficiently. Understanding the molecular basis for priming of the respiratory burst might permit its eventual therapeutic manipulation.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D006801:Humans; D008262:Macrophage Activation; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D008564:Membrane Potentials; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D019255:NADPH Oxidases; D010101:Oxygen Consumption; D010587:Phagocytosis; D011493:Protein Kinase C / Q000378:metabolism; D011951:Receptors, Complement; D011961:Receptors, Fc; D012964:Sodium / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D011961:Receptors, Fc; D013481:Superoxides; D009249:NADP; D012964:Sodium; D000242:Cyclic AMP; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium