Regulation of Fas-mediated apoptosis in neutrophils after surgery-induced acute inflammation
Regulation of Fas-mediated apoptosis in neutrophils after surgery-induced acute inflammation
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DOI：
10.1016/j.jss.2005.10.013
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发表时间：
2006-07-01
影响因子：
2.2
通讯作者：
Nagumo, Masao
中科院分区：
文献类型：
--
作者：
Iwase, Masayasu;Kondo, Gen;Nagumo, Masao
背景中性粒细胞在体外培养过程中经历快速Fas介导的凋亡。本研究的目的是探讨手术应激对循环中性粒细胞Fas介导的凋亡反应的影响。在术前2天、术后1天和术后5天，从8名下颌骨多颌畸形患者中抽取血液样本，这些患者接受了双侧下颌升支矢状劈开截骨术。然后在存在或不存在自体血浆的情况下，评价每个血液样本中循环中性粒细胞对Fas介导的凋亡的敏感性。与术前2天和术后5天相比，在FBS存在下，这些手术治疗患者的中性粒细胞中Fas诱导的凋亡在术后1天略有加速。然而，我们在自体血浆的存在下获得了不同的结果。与术前2天和术后5天的水平相比，术后第1天暴露于自体血浆后中性粒细胞中Fas诱导的凋亡反应水平被显著抑制。中性粒细胞表面的Fas表达水平没有改变，但血浆中的可溶性Fas（sFas）水平在术后期间下降到几乎相反的水平。这些患者术后第1天血浆中的粒细胞-巨噬细胞集落刺激因子、白细胞介素-6和白细胞介素-8水平也显著升高。然而，血浆对Fas介导的中性粒细胞凋亡的抗凋亡作用不受这些细胞因子的中和抗体的影响。术后血浆对Fas介导的中性粒细胞凋亡的抑制作用可被磷脂酰肌醇3-激酶（PI 3-K）抑制剂LY 294002和wortmannin阻断。此外，细胞外信号调节激酶（ERK）抑制剂PD 98059也可阻断上述作用，而p38丝裂原活化蛋白激酶抑制剂SB 203580则不能阻断上述作用。急性炎症患者血浆中sFas水平升高可能导致Fas介导的中性粒细胞凋亡受到抑制。此外，PI 3-K和ERK信号通路的激活也可能部分有助于下调。Fas介导的中性粒细胞凋亡反应。(c)2006年爱思唯尔公司All rights reserved.
Background. Neutrophils undergo rapid Fas-mediated apoptosis during in vitro culture. The purpose of this study was to investigate the effects of surgical stress upon the Fas-mediated apoptotic response in circulating neutrophils.Materials and methods. Blood samples were drawn from eight patients with a mandibular prognathism, and who had undergone a bilateral sagittal split ramus osteotomy, at 2 days before, and at 1 and 5 days after surgery. The circulating neutrophils in each blood sample were then evaluated for their susceptibility to Fas-mediated apoptosis in either the presence or the absence of autogenous plasma.Results. Fas-induced apoptosis in the neutrophils of these surgically treated patients was found to be slightly accelerated at 1 day postoperatively in the presence of FBS, compared with 2 days preoperatively and 5 days postoperatively. However, we obtained different results for these experiments in the presence of autogenous plasma. The Fas-induced apoptotic response levels in the neutrophils at day 1 postsurgery following exposure to autogenous plasma were significantly suppressed compared with the levels at both 2 days preoperatively and 5 days postoperatively. The Fas expression levels on the cell surface of the neutrophils were not altered, but the levels of soluble Fas (sFas) in the plasma were reduced to almost inverse levels during the postoperative periods. The levels of granulocyte-macrophage colony-stimulating factor, interleukin-6, and interleukin-8 levels in the plasma were also markedly raised in the plasma from each of these patients at 1 day postoperatively. However, the anti-apoptotic effects of the plasma on the Fas-mediated neutrophil apoptosis were not influenced by the addition of their neutralizing antibodies for these cytokines. The suppressive effects of postoperative plasma on Fas-mediated neutrophil apoptosis were blocked by the phosphatidylinositol 3-kinase (PI 3-K) inhibitors, LY294002, and wortmannin. Additionally, these effects were also abrogated by the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, but not by the p38 mitogen-activated protein kinase inhibitor, SB203580.Conclusions. The increase in sFas levels in the plasma of patients with acute inflammation may lead to the inhibition of Fas-mediated neutrophil apoptosis. Moreover, the activation of the PI 3-K and ERK signaling-dependent pathways may, in part, also contribute to the down-regulation. of the Fas-mediated apoptotic response in neutrophils. (c) 2006 Elsevier Inc. All rights reserved.