Significance of polymorphonuclear neutrophil cell death in surgical stress

我们研究了多形核中性粒细胞死亡在手术应激中的意义。结果表明：（1）渗出性PMN凋亡在术后第1天即受到明显抑制，随后呈时间依赖性增加。IL-6、GM-CSF与抑制渗出型PMN凋亡有关，TNF-α、IL-10与增加凋亡有关。术后早期抑制PMN凋亡，可增加渗出性PMN的ROI生成和CD 16表达。了解PMN凋亡的机制及其在局部炎症部位的病理生理学意义可能有助于设计更合理的治疗方法。(2)体外IL-6和GM-CSF可抑制健康人中性粒细胞凋亡。此外，IL-10可减弱IL-6对PMN凋亡的抑制作用。(3)低剂量活E. coli主要抑制PMN凋亡，而高剂量E.大肠杆菌增加坏死。通过抑制PMN细胞死亡，增强PMN杀菌功能可能有利于宿主防御细菌感染和/或脓毒症。(4)抗生素如ABPC、CEZ、CPZ和LMOX通过细丝形成的模式杀死细菌，导致过量的内毒素释放、细胞因子产生和PMN坏死。IMP则以原生质球方式杀灭细菌，抑制内毒素的过度释放、PMN细胞因子的产生和坏死，并诱导PMN凋亡。抗生素的选择可基于其PMN坏死诱导特性以及其敏感性谱，用于临床改善严重感染和/或脓毒症的治疗。(5)GH预处理可下调PMNs表面Fas表达，抑制PMNs凋亡，上调ROI产生。GH预处理也增加单核细胞ROI产生。虽然激活的中性粒细胞有潜在的有害方面，我们的研究结果表明，生长激素可能主要是通过增强中性粒细胞的功能寿命提高宿主的防御。

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.