INTERLEUKIN-8 PRIMING OF HUMAN NEUTROPHILS IS NOT ASSOCIATED WITH PERSISTENTLY ALTERED CALCIUM FLUXES BUT IS ADDITIVE WITH LIPOPOLYSACCHARIDE

Interleukin-8 (IL-8) priming was studied in neutrophils to examine its dependency on altered calcium fluxes and for similarity to Lipopolysa ccharide (LPS), IL-8 caused a rapid rise in [Ca2+](i) that returned to baseline values by 20 min, Peak [Ca2+](i) transients in response to N -formyl-methionyl-leucyl-phenylalanine (fMLP) were unaltered in IL-8-p rimed compared with unprimed cells, In comparison to LPS and tumor nec rosis factor (TNF), IL-8 was a much weaker priming agent as measured b y either O-2(-) or H2O2 production, Despite their large disparity in p otency, IL-8 and LPS priming were additive using fMLP, a receptor-depe ndent stimulator,; and synergistic using the post-receptor, protein ki nase C activator, phorbol 12-myristate 13-acetate (PMA) to trigger the respiratory burst, In contrast, IL-8 and TNF priming were synergistic for fMLP (P = 0.05), but completely nonadditive when PMA was used as the neutrophil stimulant (P = 0.05 for subadditivity). Thus, lasting a lterations in [Ca2+](i) are not a necessary characteristic of IL-8-pri med cells. IL-8 and LPS appear to prime by non-overlapping pathways, w hereas IL-8 and TNF appear to share mechanisms distal to protein kinas e C activation. IL-8 and LPS may independently contribute to neutrophi l-mediated host defense or injury by priming through distinct pathways .