IL-i f3 primes IL-8-activated human neutrophils for elastase release, phospholipase D activity, and calcium flux

Abstract: Interleukin-8 (IL-8), the prototype of the a (i.e., C-X-C branch) chemokine family, induced elastase release in a concentration-dependent man-ner (50-1000 ngJmL) in cytochalasin B-treated hu-man polymorphonuclear leukocytes (PMNs). This response was potentiated about twofold if PMNs were preexposed to interleukin- 1 (IL- 1 ) at concentra-tions that were by themselves inactive. The effect of IL- 1 1 was clearly observed after 5 mm and was maximal after a 30-nun preincubation of the cells. The effect was present over the whole active concen-tration range of IL-8 and was completely blocked by the presence of IL- 1 receptor antagonist. Priming of elastase release by IL- 1 was not associated with a change in receptor number or affinity for IL-8. On the contrary, it was correlated with priming of phos-pholipase D activity and calcium flux activated by IL-8. Preincubation of the cells with ethanol and/or La3 + inhibited IL-8-induced degranulation, suggest-ing that activation of phospholipase D and increase of [Ca2 + Ji were important for this response. In contrast, ethanol and La3 + did not decrease the priming effect of IL-1. IL-8 and IL-1 have been shown to be released by the same cell types and may be concomitantly present at sites of inflammation, giving rise to an amplification of the inflammator