Activation of the respiratory burst oxidase in neutrophils: on the role of membrane-derived second messengers, Ca++, and protein kinase C.
A major bactericidal mechanism of neutrophils involves activation of the respiratory burst oxidase to generate superoxide (O2-). The oxidase is activated rapidly, often within a minute, in response to extracellular signals such as chemoattractants, inflammatory mediators, and invading microorganisms. Increasing evidence indicates that lipases also respond rapidly, releasing potent regulatory molecules from progenitor lipids. Released molecules include potential regulators of protein kinase C--diacylglycerol (DAG), arachidonate, and sphingosine--and levels of one of these, DAG, frequently correlate with O2- production. In this author's view, the available data implicate DAG and protein kinase C as key factors in the regulation of the respiratory burst. Herein, the array of activating agonists, the generation and function of some lipid-derived mediators, and evidence pertaining to the participation of protein kinase C are reviewed.
Lambeth
J D
JD
Department of Biochemistry, Emory University Medical School, Atlanta, Georgia 30322.
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000097:blood*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology*; D011493:Protein Kinase C / Q000097:blood*; D015290:Second Messenger Systems; D013481:Superoxides / Q000097:blood*
D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme; D011493:Protein Kinase C