ROLE OF CHEMOTACTIC FACTOR INACTIVATION IN NEUTROPHIL CHEMOTAXIS

Abstract

CFI [chemotactic factor inactivator] has been implicated in the regulation of several inflammatory mediators; consequently, the effects of CFI on neutrophil chemotactic and lysosomal enzyme release responses to C5[complement component 5]-derived chemotaxins were evaluated. Chemotaxis was measured by directed migration under agarose, LER [neutrophil lysosomal enzyme release] by glucosaminidase release from cytochalasin B-treated neutrophil, and CFI activity by its inhibition of LER. After inactivation by CFI, C5-fr [C5-derived chemotactic fractions] 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 MW. Effects of CFI on neutrophil responses to C5-fr, ZAS [zymosan-activated serum] and ZAP [zymosan-activated plasma] were adverse and dose-dependent; maximal neutrophil response to C5-fr decreased in amplitude as CFI levels increased, and a close reciprocal relationship was demonstrated between the endogenous CFI and the chemotactic activities of ZAS (r = -0.833) and ZAP (r = -0.932) in 10 healthy [human] adults. CFI probably is a potent regulator of neutrophil response to C5-derived inflammatory mediators.