Leuenroth S, Lee C, Grutkoski P, Keeping H, Simms H H
Brown University School of Medicine, Rhode Island Hospital, Department of Surgery, Providence 02903, USA.
Surgery. 1998 Aug;124(2):409-17.
Neutrophil apoptosis is crucial in the resolution of inflammation. The role of interleukin (IL)-8 in neutrophil apoptosis has not been previously studied; we hypothesized that in addition to its role as a chemoattractant, IL-8 would regulate polymorphonuclear leukocyte (PMN) apoptosis.
PMNs were adhered to plastic during hypoxia or normoxia and treated with IL-8 dosages of 0 to 1000 ng/mL. Apoptosis was assessed by cellular histology and the TUNEL assay. For receptor inhibition, blocking antibodies to IL-8 receptors in the presence of IL-8 were added. Apoptosis of PMNs treated with anti-Fas antibody +/- IL-8 was also analyzed.
After treatment with 100 ng/mL IL-8 apoptosis was decreased from an average of 39.1% 9.3%. Inhibition of IL-8RA was able to restore apoptosis to 59.4%. Western analysis showed that with IL-8, there was a marginal decrease of total Fas protein, whereas Fas ligand was increased. After incubation with an apoptosis inducing-Fas antibody plus IL-8 reduced apoptosis to 9.5%.
IL-8 not only promotes the inflammatory response by recruiting PMNs but also acts to suppress apoptosis mainly through the IL-8RA in an oxygen tension independent manner. The reduction in apoptosis is associated with changes in Fas and FasL where the presence of IL-8 suppresses the proapoptotic function of Fas-FasL interactions.
中性粒细胞凋亡在炎症消退过程中至关重要。白细胞介素（IL）-8在中性粒细胞凋亡中的作用此前尚未得到研究；我们推测，IL-8除了作为趋化因子发挥作用外，还会调节多形核白细胞（PMN）凋亡。
在缺氧或常氧条件下，将PMN贴附于塑料表面，并用0至1000 ng/mL的IL-8剂量进行处理。通过细胞组织学和TUNEL检测评估凋亡情况。为进行受体抑制，在存在IL-8的情况下添加针对IL-8受体的阻断抗体。还分析了用抗Fas抗体+/-IL-8处理的PMN的凋亡情况。
用100 ng/mL IL-8处理后，凋亡率从平均39.1%降至9.3%。抑制IL-8RA能够使凋亡率恢复至59.4%。蛋白质免疫印迹分析显示，使用IL-8后，Fas总蛋白略有减少，而Fas配体增加。用凋亡诱导Fas抗体孵育并加入IL-8后，凋亡率降至9.5%。
IL-8不仅通过募集PMN促进炎症反应，还主要通过IL-8RA以氧张力独立的方式抑制凋亡。凋亡减少与Fas和FasL的变化有关，其中IL-8的存在抑制了Fas-FasL相互作用的促凋亡功能。
