Abraham Edward
Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine,University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Proc Am Thorac Soc. 2005;2(3):243-7. doi: 10.1513/pats.200501-004AC.
Alterations in the generation of activated protein C (APC) as well as in the interactions of APC with the endothelial protein C receptor are present in severe sepsis and acute lung injury. Administration of recombinant human activated protein C (rhAPC) improves the survival of critically ill patients with sepsis, but the mechanisms by which rhAPC produces benefit are not well defined. Human models of systemic and pulmonary endotoxin exposure may provide important insights into the mechanisms of action of rhAPC in critical illness. In volunteers given systemic endotoxin, rhAPC had minimal effects on physiologic parameters, including blood pressure, markers of inflammation, and measures of sepsis-induced coagulopathy. In contrast, in the setting of pulmonary endotoxin exposure, rhAPC decreased neutrophil migration into the airspaces and also diminished neutrophil chemotaxis. Administration of rhAPC did not affect other parameters of neutrophil function, including kinase activation, production of proinflammatory cytokines, or apoptosis. Such results indicate that the effects of rhAPC in inhibiting the infiltration of neutrophils into the lungs and other inflammatory sites may contribute to its beneficial effects in sepsis.
严重脓毒症和急性肺损伤时，活化蛋白C（APC）生成以及APC与内皮细胞蛋白C受体相互作用均发生改变。给予重组人活化蛋白C（rhAPC）可提高脓毒症危重症患者的生存率，但其产生有益作用的机制尚不清楚。全身性和肺部内毒素暴露的人体模型可能为深入了解rhAPC在危重症中的作用机制提供重要线索。在给予全身性内毒素的志愿者中，rhAPC对生理参数（包括血压、炎症标志物和脓毒症诱导的凝血病指标）影响极小。相比之下，在肺部内毒素暴露情况下，rhAPC可减少中性粒细胞向肺泡腔的迁移，并降低中性粒细胞趋化性。给予rhAPC不影响中性粒细胞功能的其他参数，包括激酶激活、促炎细胞因子产生或凋亡。这些结果表明，rhAPC抑制中性粒细胞向肺部及其他炎症部位浸润的作用可能有助于其在脓毒症中的有益作用。
