Priming of the neutrophil respiratory burst is species-dependent and involves MAP kinase activation

Background. Priming of the neutrophil respiratory burst hers been implicate d in the pathogenesis of multi-system organ failure (MSOF) after sepsis and trauma. The intracellular signal transduction pathways that mediate primin g are unclear. Methods. Human, porcine, rabbit, rat, and mouse neutrophils were assayed by luminol-dependent chemiluminescence in whole blood and purified neutrophil preparations. Multiple priming agents and agonists were studied as was inh ibition of priming by the p38 mitogen-activated protein kinase (MAPK) inhib itor SB203580 and the Mek 1/2 inhibitor PD98059. Results. Priming by tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was s ignificantly inhibited by SB203580, whereas platelet-activating factor (PAF ) priming was unaffected. Neither TNF-alpha nor PAF primed polymorphonuclea r neutrophils (PMNs) within whole blood for N-formyl-methionyl-leucyl-pheny lalanine (f-MLP) activation, in contrast to activation by complement-opsoni zed zymosan (OPZ) or low-dose phorbolmyristate acetate (PMA). Both TNF-alph a and PAF however; primed purified neutrophils for f-MLP activation. In con trast to human and porcine PMNs, rabbit, rat, and mouse PMNs could not be p rimed by TNF-alpha or PAF, regardless of the final agonist. Conclusions. Priming of the PMN respiratory burst proceeds through multiple signaling pathways, depending on the particular priming agent and agonist pair Differences in priming between PMNs in whole blood and purified prepar ations may be physiologically significant. There is a pronounced species de pendency in the ability to prime the neutrophil respiratory burst.