POSTINJURY NEUTROPHIL PRIMING AND ACTIVATION STATES - THERAPEUTIC CHALLENGES

Both hyperactivity and hypoactivity of neutrophils (PMNs) have been im plicated in the pathogenesis of postinjury multiple organ failure. In this paper, the cellular and molecular mechanisms involved in the regu lation of PMN O-2(-) production are reviewed. In addition, relevant re search laboratory techniques for measuring both intracellular and extr acellular O-2(-) release are outlined. In a pilot study PMN O-2(-) rel ease in response to a battery of PMN agonists was determined, and four functional states of the NADPH were defined: resting, primed, activat ed, and unresponsive. PMNs from normal adult volunteers are in the res ting state. In contrast, PMNs from patients with severe torso trauma a re primed and activated in the first 24 h postinjury, but, after 48 h, become unresponsive to both receptor-dependent (platelet activating f actor and N-formyl-methyl-leucyl-phenylalanine) and receptor-independe nt (phorbol 12-myristate 13-acetate) activation. The ability to identi fy at-risk patients and provide a rationale for ameliorating PMN-media ted tissue injury in patients with hyperinflammation syndromes are dis cussed. In addition, the importance of identifying patients with PMNs that are unresponsive, and the necessity far increasing PMN function i n these patients in order to reduce the risk of sepsis, are also discu ssed.