POSTINJURY NEUTROPHIL PRIMING AND ACTIVATION - AN EARLY VULNERABLE WINDOW

Background. Generation of extracellular, cytotoxic superoxide anion (O -2(-)) by polymorphonuclear neutrophils (PMNs) contributes to an unbri dled inflammatory response that can precipitate multiple organ failure (MOF). Release of O-2(-) is markedly enhanced when activated PMNs hav e been previously ''primed'' by inflammatory mediators, such as those expressed after trauma. We therefore hypothesized that PMN priming occ urs as an integral part of the early inflammatory response to trauma. Methods. PMNs were obtained from 17 high-risk patients with torso trau ma at 3, 6, 12, 24, 48, and 72 hours after injury, as well as from 10 healthy donors, and the in vitro release of O-2(-) was quantitated wit h a kinetic, superoxide dismutase (SOD)-inhibitable cytochrome c reduc tion assay. PMN O-2(-) release was measured in the presence and absenc e of 1 mu mol/L N-formyl-methionyl-leucyl-phenylalamine (fMLP) and aft er priming and activation with 20 nmol/L platelet-activating factor (P AF) and 1 mu mol/L fMLP, respectively. Results. In vitro PMN O-2(-) re lease was used to determine whether postinjury PMNs were (1) activated in vivo, (2) primed in vivo, or (3) primable in vitro. Unstimulated P MNs from trauma patients spontaneously expressed modest amounts of O-2 (-) in vitro from 6 to 48 hours after injury, suggesting endogenous ac tivation. Also, fMPL-activated PMNs collected between 3 and 24 hours a fter injury expressed more O-2(-) than controls (p less than or equal to 0.02), indicating in vivo, trauma-related priming. Furthermore, pos tinjury PMNs were maximally primed in vivo (i.e., in vitro exposure to PAF before fMLP activation failed to significantly enhance O-2(-) rel ease) as compared to PMNs treated with fMLP. Conclusions. These data i ndicate that major torso trauma (first hit) primes and activates PMNs within 3 to 6 hours after injury. Consequently, we postulate that post injury priming of PMNs may create an early vulnerable window during wh ich a second hit (e.g., a secondary operation or delayed hemorrhage) a ctivates exuberant PMN O-2(-) release, rendering the injured patient a t high risk for MOF.