Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure.
Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure.
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发表时间：
1996-05
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通讯作者：
D. Partrick;F. Moore;Ernest E. Moore;C. Barnett;C. Silliman
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作者：
D. Partrick;F. Moore;Ernest E. Moore;C. Barnett;C. Silliman
与早期的感染模型相比，对多器官衰竭（MOF）的持续研究导致了组织损伤的炎症模型的发展。这种焦点的变化是对最近临床观察的反应，这些观察表明损伤后MOF经常在没有感染的情况下发生。在已经提出的替代性“两次打击”炎症模型中，最初的创伤性损伤“引发”炎症反应，使得延迟的、否则无害的炎症性损伤触发夸大的反应。中性粒细胞（PMN），独特的装备，通过烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶系统引起氧化性组织损伤，已被牵连作为一个早期的关键球员在这个模型的损伤后MOF。与“两次打击”炎症模型相似，循环中的中性粒细胞通过对增强的超氧阴离子（O2）进行激发来响应促炎介质。通过增加对易受PMN介导的损伤的器官的内皮的粘附。随后的促炎性损伤促进进一步的中性粒细胞隔离，并激活它们以增强O2的释放。由此产生的组织损伤可能会持续下去，并导致最终的终末器官损伤和衰竭。在NADPH氧化酶系统方面，各种激动剂引起的PMN引发和激活已在体外得到充分证明，并导致内皮损伤增加。PMN引发和激活也可在肠道缺血/再灌注的体内模型中操作，这是休克和创伤复苏的替代物，导致远端器官损伤。最后，在严重创伤患者的临床研究中，PMN启动和激活序列可识别出有发生MOF风险的患者及其相关的高死亡率。进一步表征创伤患者中调节PMN引发和激活的机制对于开发新的治疗干预措施是必要的，所述新的治疗干预措施旨在阻断导致MOF的有害PMN反应，同时不损害宿主防御和组织修复的有益PMN功能。
The continuing study of multiple organ failure (MOF) has led to the development of inflammatory models of tissue injury in contrast to earlier infectious models. This change of focus is in response to more recent clinical observations suggesting that postinjury MOF frequently occurs in the absence of infection. In the alternative "two-hit" inflammatory model that has been proposed, the initial traumatic insult "primes" the inflammatory response such that a delayed, otherwise innocuous, inflammatory insult triggers an exaggerated response. The neutrophil (PMN), being uniquely equipped to cause oxidative tissue injury via the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, has been implicated as an early pivotal player in this model of postinjury MOF. Similar to the "two-hit" inflammatory model, circulating PMNs respond to proinflammatory mediators by becoming primed for enhanced superoxide anion (O2.) production and by increasing adherence to endothelium of organs that are susceptible to PMN-mediated injury. Subsequent proinflammatory insults promote further neutrophil sequestration and activate them for enhanced release of O2.-. The resulting tissue injury can be perpetuated and lead to eventual end-organ damage and failure. In terms of the NADPH oxidase system, PMN priming and activation by various agonists have been well documented in vitro and lead to increased endothelial damage. PMN priming and activation are also operable in an in vivo model of gut ischemia/reperfusion, a surrogate of shock and trauma resuscitation, leading to distant organ damage. Finally, in clinical studies of severely injured trauma patients, PMN priming and activation sequences identify patients at risk for developing MOF with its associated high mortality. Further characterization of the mechanisms that regulate PMN priming and activation in the trauma patient is necessary for the development of new therapeutic interventions designed to block deleterious PMN responses which lead to MOF while not compromising beneficial PMN functions of host defense and tissue repair.