POSTINJURY NEUTROPHIL PRIMING AND ACTIVATION - AN EARLY VULNERABLE WINDOW
POSTINJURY NEUTROPHIL PRIMING AND ACTIVATION - AN EARLY VULNERABLE WINDOW
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DOI：
10.1016/s0039-6060(05)80345-9
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发表时间：
1995-08-01
期刊：
影响因子：
3.8
通讯作者：
PETERSON, VM
中科院分区：
文献类型：
--
作者：
BOTHA, AJ;MOORE, FA;PETERSON, VM
背景多形核中性粒细胞（PMN）产生细胞外的细胞毒性超氧阴离子（O-2（-）），导致无节制的炎症反应，可加速多器官衰竭（MOF）。当激活的中性粒细胞预先被炎症介质（如创伤后表达的介质）“引发”时，O-2（-）的释放显著增强。因此，我们假设中性粒细胞启动作为创伤早期炎症反应的一个组成部分。从17例躯干创伤的高危患者以及10例健康供体中获得伤后3、6、12、24、48和72小时的PMN，并采用动力学超氧化物歧化酶（SOD）-还原性细胞色素c还原试验定量体外释放O-2（-）。分别用20 nmol/L血小板活化因子（PAF）和1 μ mol/L fMLP预激和活化后，测定1 μ mol/L fMLP和1 μ mol/L fMLP存在和不存在时PMN O-2（-）释放。体外PMN O-2（-）释放用于确定损伤后PMN是否（1）在体内活化，（2）在体内引发，或（3）在体外引发。创伤患者的未受刺激的PMNs在体外从损伤后6到48小时自发表达适量的O-2（-），表明内源性激活。此外，在损伤后3至24小时收集的fMPL激活的PMN表达的O-2（-）比对照组多（p小于或等于0.02），表明在体内，创伤相关的启动。此外，损伤后PMN在体内被最大程度地引发（即，与用fMLP处理的PMN相比，在体外暴露于PAF之前，fMLP激活未能显著增加O-2（-）释放。这些数据表明，主要的躯干创伤（第一次击中）启动和激活中性粒细胞在受伤后3至6小时内。因此，我们假设，伤后中性粒细胞的启动可能会产生一个早期脆弱的窗口，在此期间，第二次打击（例如，二次手术或迟发性出血）激活了旺盛的PMN O-2（-）释放，使受伤的患者处于MOF的高风险中。
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.