Activation of neutrophil leukocytes: chemoattractant receptors and respiratory burst

The human organism survives the constant attack by bacteria and other pathogens thanks to the surveillance function of the neutrophil leukocytes. At sites of infection, several messenger molecules are generated that attract neutrophils from the blood and direct their migration toward the microbes, a process termed chemotaxis. Neutrophils sense chemotactic agonists through a group of closely related, GTP-binding protein-coupled receptors. Several of these have been recently cloned and shown to belong to the superfamily of rhodopsin-like, seven-transmembrane-domain receptors. At the site of infection, the neutrophils engulf and kill the invading microbes. This critical function depends on the production of superoxide and related radicals by a tightly regulated, membrane-bound NADPH oxidase that is activated by chemotactic agonists and other inflammatory stimuli. The characteristics of the receptors as well as new insights into the mechanism of activation of the superoxide-forming oxidase as presented at a recent FASEB meeting symposium are reviewed.