Significance of polymorphonuclear neutrophil cell death in surgical stress

我们探讨了手术应激中多形核中性粒细胞死亡的意义。结果表明：(1)术后第1天，渗出性PMN细胞凋亡明显受到抑制，并呈时间依赖性增加。IL-6和GM-CSF与抑制渗出性PMN凋亡有关，TNF-a和IL-10与增加细胞凋亡有关。术后早期抑制PMN凋亡，可增加渗出性PMN的ROI产生和CD16表达。了解PMN凋亡的机制及其在体内局部炎症部位的病理生理意义可能有助于设计更合理的治疗方法。(2) IL-6和GM-CSF对健康志愿者PMN细胞凋亡的抑制作用。IL-10降低了IL-6对PMN细胞凋亡的抑制作用。(3)低剂量活大肠杆菌主要抑制PMN凋亡，而高剂量大肠杆菌则增加坏死。增强PMN杀菌功能，通过抑制PMN细胞死亡，可能有利于宿主防御细菌感染和/或败血症。(4) ABPC、CEZ、CPZ、LMOX等抗生素通过成丝方式杀死细菌，导致PMNs过度释放内毒素，产生细胞因子，导致PMNs坏死。相比之下，IMP通过球质体模式杀死细菌，抑制过多的内毒素释放、PMN细胞因子的产生和坏死，并诱导PMN凋亡。抗生素的选择可能基于其诱导PMN坏死的特性以及对严重感染和/或败血症治疗的临床改善的敏感谱。(5) GH预处理可下调PMNs中Fas的表达，抑制细胞凋亡，上调PMNs的ROI生成。生长激素预处理也增加单核细胞ROI的产生。虽然活化的PMN有潜在的有害方面，但我们的研究结果表明，生长激素可能主要通过增加PMN的功能寿命来改善宿主防御。

We investigated the significance of polymorphonuclear neutrophil cell death in surgical stress. Obtained results are as follows :(1) Exudative PMN apoptosis was markedly inhibited on postoperative day 1 and then increased in a time-dependent manner. IL-6 and GM-CSF were related to inhibit exudative PMN apoptosis, while TNF-a and IL-10 were related to increase apoptosis. ROI production and CD16 expression of exudative PMNs were augmented when PMN apoptosis was inhibited in the early postoperative period. Understanding the mechanisms of PMN apoptosis and its pathophysiological significance at local inflammatory sites in vivo may help in the design of more rational treatments.(2) In vitro IL-6 and GM-CSF inhibited apoptosis of PMN isolated from healthy volunteers. Moreover, IL-10 reduced the inhibitory effect of IL-6 on PMN apoptosis.(3) Low doses of live E. coli inhibits predominantly PMN apoptosis, whereas a high dose of E. coli increases necrosis. Augmented PMN bactericidal function, via inhibition of PMN cell death, may be beneficial for host defense against bacterial infection and/or sepsis.(4) Antibiotics such as ABPC, CEZ, CPZ and LMOX kill bacteria by a mode of filament formation, leading to excessive endotoxin release, cytokine production and necrosis of PMNs. In contrast, IMP, killing bacteria by a mode of spheroplast, inhibit excessive endotoxin release, PMN cytokine production, and necrosis, and induced PMN apoptosis. Antibiotic choices may be based on their PMN necrosis inducing property as well as their sensitivity spectrum for the clinical improvement of therapy of severe infection and/or sepsis.(5) GH pretreatment downregulates Fas expression on PMNs, inhibits apoptosis and upregulates ROI producdon of PMNs. GH pretreatment also increases monocyte ROI production. Although activated PMNs have potentially harmful aspects, our results suggest that GH may improve host defense mainly through enhancement of the PMN functional life span.