POSTINJURY NEUTROPHIL PRIMING AND ACTIVATION - AN EARLY VULNERABLE WINDOW

被引:203
作者
BOTHA, AJ
MOORE, FA
MOORE, EE
KIM, FJ
BANERJEE, A
PETERSON, VM
机构
[1] DENVER GEN HOSP,DEPT SURG,DENVER,CO 80204
[2] UNIV COLORADO,HLTH SCI CTR,DENVER,CO
关键词
D O I
10.1016/S0039-6060(05)80345-9
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Generation of extracellular, cytotoxic superoxide anion (O-2(-)) by polymorphonuclear neutrophils (PMNs) contributes to an unbridled inflammatory response that can precipitate multiple organ failure (MOF). Release of O-2(-) is markedly enhanced when activated PMNs have been previously ''primed'' by inflammatory mediators, such as those expressed after trauma. We therefore hypothesized that PMN priming occurs as an integral part of the early inflammatory response to trauma. Methods. PMNs were obtained from 17 high-risk patients with torso trauma 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 with a kinetic, superoxide dismutase (SOD)-inhibitable cytochrome c reduction assay. PMN O-2(-) release was measured in the presence and absence of 1 mu mol/L N-formyl-methionyl-leucyl-phenylalamine (fMLP) and after priming and activation with 20 nmol/L platelet-activating factor (PAF) and 1 mu mol/L fMLP, respectively. Results. In vitro PMN O-2(-) release was used to determine whether postinjury PMNs were (1) activated in vivo, (2) primed in vivo, or (3) primable in vitro. Unstimulated PMNs from trauma patients spontaneously expressed modest amounts of O-2(-) in vitro from 6 to 48 hours after injury, suggesting endogenous activation. Also, fMPL-activated PMNs collected between 3 and 24 hours after injury expressed more O-2(-) than controls (p less than or equal to 0.02), indicating in vivo, trauma-related priming. Furthermore, postinjury PMNs were maximally primed in vivo (i.e., in vitro exposure to PAF before fMLP activation failed to significantly enhance O-2(-) release) as compared to PMNs treated with fMLP. Conclusions. These data indicate that major torso trauma (first hit) primes and activates PMNs within 3 to 6 hours after injury. Consequently, we postulate that postinjury priming of PMNs may create an early vulnerable window during which a second hit (e.g., a secondary operation or delayed hemorrhage) activates exuberant PMN O-2(-) release, rendering the injured patient at high risk for MOF.
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页码:358 / 365
页数:8
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