title: Postinjury neutrophil priming and activation states: therapeutic challenges.
abstract: Both hyperactivity and hypoactivity of neutrophils (PMNs) have been implicated in the pathogenesis of postinjury multiple organ failure. In this paper, the cellular and molecular mechanisms involved in the regulation of PMN O2- production are reviewed. In addition, relevant research laboratory techniques for measuring both intracellular and extracellular O2- release are outlined. In a pilot study PMN O2- release in response to a battery of PMN agonists was determined, and four functional states of the NADPH were defined: resting, primed, activated, and unresponsive. PMNs from normal adult volunteers are in the resting state. In contrast, PMNs from patients with severe torso trauma are primed and activated in the first 24 h postinjury, but, after 48 h, become unresponsive to both receptor-dependent (platelet activating factor and N-formyl-methyl-leucyl-phenylalanine) and receptor-independent (phorbol 12-myristate 13-acetate) activation. The ability to identify at-risk patients and provide a rationale for ameliorating PMN-mediated tissue injury in patients with hyperinflammation syndromes are discussed. In addition, the importance of identifying patients with PMNs that are unresponsive, and the necessity for increasing PMN function in these patients in order to reduce the risk of sepsis, are also discussed.
authors.forename: A J
authors.initials: AJ
authors.lastname: Botha
authors.forename: F A
authors.initials: FA
authors.lastname: Moore
authors.forename: E E
authors.initials: EE
authors.lastname: Moore
authors.forename: B
authors.initials: B
authors.lastname: Fontes
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.forename: V M
authors.initials: VM
authors.lastname: Peterson
mesh_terms: D006801:Humans; D009102:Multiple Organ Failure / Q000201:enzymology / Q000378:metabolism* / Q000628:therapy*; D009247:NADH, NADPH Oxidoreductases; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D014947:Wounds and Injuries / Q000201:enzymology / Q000378:metabolism* / Q000628:therapy*
chemical_list: D009247:NADH, NADPH Oxidoreductases