Role of chemotactic factor inactivation in neutrophil chemotaxis.
CFIs have been implicated in the regulation of several inflammatory mediators; consequently, we have evaluated the effects of CFI on neutrophil chemotactic and lysosomal enzyme release response to C5-derived chemotaxins. Chemotaxis was measured by direct migration under agarose, LER by glucosaminidase release from cytochalasin B-treated neutrophils, and CFI activity by its inhibition of LER. After inactivation by CFI, C5-fr lost their ability to stimulate neutrophils, and acquired a new chemotactic inhibitory activity. On gel chromatography, the stimulatory activity of C5-fr and the inhibitory activity of inactivated C5-fr eluted as separate peaks with different molecular weights. Effects of CFI on neutrophil responses to C5-fr, ZAS, and ZAP were adverse and dose-dependent: maximal neutrophil response to C5-ft decreased in amplitude as CFI levels increased, and a close reciprocal relationship was demonstrated between the endogenous CFI and the chemotaxis activities of ZAS (r = -0.833) and ZAP (r = -0.932) in 10 healthy adults. The data suggest that CFI is a potent regulator of neutrophil response to C5-derived inflammatory mediators.
D000328:Adult; D000626:Aminopeptidases; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors* / Q000097:blood / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D009504:Neutrophils
D002630:Chemotactic Factors; C010073:chemotactic factor inactivator; D000626:Aminopeptidases