IL-1-BETA PRIMES IL-8-ACTIVATED HUMAN NEUTROPHILS FOR ELASTASE RELEASE, PHOSPHOLIPASE-D ACTIVITY, AND CALCIUM FLUX

Interleukin-8 (IL-8), the prototype of the alpha (i.e., C-X-C branch) chemokine family, induced elastase release in a concentration-dependen t manner (50-1000 ng/mL) in cytochalasin B-treated human polymorphonuc lear leukocytes (PMNs). This response was potentiated about twofold if PMNs were preexposed to interleukin-1 beta (IL-1 beta) at concentrati ons that were by themselves inactive. The effect of IL-1 beta was clea rly observed after 5 min and was maximal after a 30-min preincubation of the cells. The effect was present over the whole active concentrati on range of IL-8 and was completely blocked by the presence of IL-1 re ceptor antagonist. Priming of elastase release by IL-1 beta was not as sociated with a change in receptor number or affinity for IL-8. On the contrary, it was correlated with priming of phospholipase D activity and calcium flux activated by IL-8. Preincubation of the cells with et hanol and/or La3+ inhibited IL-8-induced degranulation, suggesting tha t activation of phospholipase D and increase of [Ca2+]i were important for this response, In contrast, ethanol and La3+ did not decrease the priming effect of IL-1 beta. IL-8 and IL-1 beta have been shown to be released by the same cell types and may be concomitantly present at s ites of inflammation, giving rise to an amplification of the inflammat ory response.