PMID: 7514637Jun 1, 1994Paper

Zymosan-induced IL-8 release from human neutrophils involves activation via the CD11b/CD18 receptor and endogenous platelet-activating factor as an autocrine modulator

The Journal of Immunology : Official Journal of the American Association of Immunologists
B T AuP D Collins

Abstract

We have investigated mechanisms that regulate the generation of IL-8 by human neutrophils on contact with zymosan particles in vitro. Zymosan stimulated IL-8 production, which increased with increasing particle numbers and was abolished by the protein synthesis inhibitor cycloheximide. IL-8 was detectable in culture supernatant at 8 h reaching a maximum at 24 h. In all further experiments IL-8 was measured at 24 h. mAbs to neutrophil CD18 (60.3 and 6.5E) caused a marked suppression of IL-8 generation, but only if added up to 2 h after zymosan stimulation. An anti-CD11b mAb (KIM 225) substantially inhibited zymosan-induced IL-8 release. We investigated whether other mediators generated during phagocytosis modulate IL-8 production. Two selective platelet-activating factor (PAF) receptor antagonists, WEB 2086 and UK 74505, produced a profound suppression of IL-8 generation, when added within 30 min to 1 h of zymosan stimulation. An IL-1R antagonist, a leukotriene B4 antagonist, and an anti-TNF-alpha Ab had no effect on IL-8 generation. FMLP, PAF, and a stable PAF agonist did not stimulate significant IL-8 production, however, a calcium ionophore (A23187) did induce IL-8 release and this was suppressed by UK 74505. We conclude that...Continue Reading

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