Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock
Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock
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DOI：
10.1164/rccm.200203-217oc
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发表时间：
2002-12-01
影响因子：
24.7
通讯作者：
Pugin, J
中科院分区：
文献类型：
--
作者：
Fumeaux, T;Pugin, J
许多重症患者的单核细胞显示低水平的主要组织相容性复合体11型（MHC II）表达。这种现象被认为在这些患者对继发感染的易感性增加中起作用。在本研究中，我们发现单核细胞人类白细胞抗原（HLA）-DR表达水平与脓毒症综合征的严重程度呈负相关。单核细胞HLA-DR表达的缺陷在于MHC II分子的细胞内隔离，这是一种翻译后效应。HLA-DR或其主要转录诱导物11类反式激活因子的转录速率没有显著降低。感染性休克患者单核细胞产生的HLA-DR蛋白水平与健康志愿者相当。感染性休克患者的血浆诱导了显著的HLA-DR内吞作用，导致正常供体单核细胞表面HLA-DR表达降低。这种作用可被抗白细胞介素（IL）-10单克隆抗体部分阻断，但不能被转化生长因子-β（1）拮抗剂、野牡丹素或β-肾上腺素能激动剂阻断。总之，这些数据表明，HLA-DR分子被重新内吞并保留在感染性休克患者的单核细胞内，并且这种现象部分由IL-10介导。IL-10可能是脓毒症综合征患者或有感染风险的重症患者免疫调节的未来靶点。
Monocytes from many critically ill patients show a low level of major histocompatibility complex type 11 (MHC II) expression. This phenomenon is believed to play a role in these patients' increased susceptibility to secondary infections. In the present study, we show that the level of monocyte human leukocyte antigen (HLA)-DR expression inversely correlates with the degree of severity of the sepsis syndrome. The defect of the monocyte HLA-DR expression resides in an intracellular sequestration of the MHC II molecules, a posttranslational effect. No significant decrease in the rate of transcription of HLA-DR, or its major transcriptional inducer, Class 11 transactivator, was noted. The levels of HLA-DR protein produced by monocytes from patients with septic shock were comparable to those from healthy volunteers. Plasma from patients with septic shock induced significant HLA-DR endocytosis resulting in decreased surface HLA-DR expression of normal donor monocytes. This effect was partially blocked by anti-interleukin (IL)-10 monoclonal antibody, but not by antagonists to transforming growth factor-beta(1), prostaglandins, or beta-adrenergic agonists. Altogether, these data suggest that HLA-DR molecules are re-endocytosed and retained intracellularly in monocytes from patients with septic shock, and that this phenomenon is partially mediated by IL-10. IL-10 may represent a future target for immunomodulating patients with the sepsis syndrome or critically ill patients at risk of developing infections.