Alves-Filho José C, de Freitas Andressa, Spiller Fernando, Souto Fabrício O, Cunha Fernando Q
Shock. 2008 Oct;30 Suppl 1:3-9. doi: 10.1097/SHK.0b013e3181818466.
Neutrophils are key effectors of the innate immune response. Reduction of neutrophil migration to infection sites is associated with a poor outcome in sepsis. We have demonstrated a failure of neutrophil migration in lethal sepsis. Together with this failure, we observed more bacteria in both peritoneal exudates and blood, followed by a reduction in survival rate. Furthermore, neutrophils obtained from severe septic patients displayed a marked reduction in chemotactic response compared with neutrophils from healthy subjects. The mechanisms of neutrophil migration failure are not completely understood. However, it is known that they involve systemic Toll-like receptor activation by bacteria and/or their products and result in excessive levels of circulating cytokines/chemokines. These mediators acting together with LPS stimulate expression of iNOS that produces high amounts of NO, which in turn mediates the failure of neutrophil migration. NO reduced expression of CXCR2 on neutrophils and the levels of adhesion molecules on both endothelial cells and neutrophils. These events culminate in decreased endothelium-leukocyte interactions, diminished neutrophil chemotactic response, and neutrophil migration failure. Additionally, the NO effect, at least in part, is mediated by peroxynitrite. In this review, we summarize what is known regarding the mechanisms of neutrophil migration impairment in severe sepsis.
中性粒细胞是先天性免疫反应的关键效应细胞。中性粒细胞向感染部位迁移的减少与脓毒症的不良预后相关。我们已经证明在致死性脓毒症中中性粒细胞迁移存在障碍。伴随着这种障碍，我们在腹膜渗出液和血液中均观察到更多细菌，随后存活率降低。此外，与健康受试者的中性粒细胞相比，重症脓毒症患者的中性粒细胞趋化反应明显降低。中性粒细胞迁移障碍的机制尚未完全明了。然而，已知其涉及细菌和/或其产物引起的全身Toll样受体激活，并导致循环细胞因子/趋化因子水平过高。这些介质与脂多糖共同作用刺激诱导型一氧化氮合酶（iNOS）的表达，产生大量一氧化氮（NO），进而介导中性粒细胞迁移障碍。NO降低了中性粒细胞上CXCR2的表达以及内皮细胞和中性粒细胞上黏附分子的水平。这些事件最终导致内皮细胞与白细胞相互作用减少、中性粒细胞趋化反应减弱以及中性粒细胞迁移障碍。此外，NO的作用至少部分是由过氧亚硝酸盐介导的。在本综述中，我们总结了关于重症脓毒症中中性粒细胞迁移受损机制的已知情况。
