Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation.

Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation.
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DOI:
10.1186/cc8959
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发表时间:
2010
期刊:
Critical care (London, England)
影响因子:
--
通讯作者:
Adib-Conquy M
Adib-Conquy M
中科院分区:
其他
文献类型:
--
作者:
Kim OY;Monsel A;Bertrand M;Coriat P;Cavaillon JM;Adib-Conquy M

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单核细胞上人类白细胞抗原II类(HLA-DR)表达减少是全身炎症反应综合征(SIRS)患者免疫状态改变的标志。到目前为止,分析主要是在不考虑单核细胞亚群的情况下进行的。我们研究了20例接受腹主动脉手术(AAS)的SIRS患者、20例接受颈动脉手术(CAS)的患者和9例健康对照者的CD 14 HIGH和CD 14 LOW单核细胞的这种修饰,并研究了可能参与此过程的介质和细胞内分子。CD 14 HIGH单核细胞上的HLA-DR在手术期间、血液再灌注后开始减少,并且在手术后进一步减少。相比之下,CD 14 LOW细胞上的HLA-DR表达仅在手术后降低,并且程度低于CD 14 HIGH单核细胞。两个亚群的HLA-DR表达的减少和皮质醇水平的变化之间存在负相关性,而白细胞介素-10(IL-10)水平和HLA-DR调节之间的负相关性仅在CD 14 HIGH细胞中观察到。根据这些离体结果,健康供体的CD 14 HIGH和CD 14 LOW单核细胞上的HLA-DR在与氢化可的松孵育后减少,而IL-10仅作用于CD 14 HIGH亚群。此外,流式细胞术显示IL-10受体在CD 14 HIGH单核细胞上的表达高于CD 14 LOW单核细胞。此外,氢化可的松,并在较小程度上IL-10,逆转了由细菌产物诱导的HLA-DR的上调。最后,膜相关的RING-CH-1蛋白(MARCH 1)mRNA,MHC II类的负调节,在AAS患者的单核细胞在术后第1天上调,并在健康受试者暴露于氢化可的松。这项研究表明,HLA-DR表达的调制不同的CD 14高(经典)与CD 14低(炎症)单核细胞后,全身炎症。
Decreased expression of human leukocyte antigen class II (HLA-DR) on monocytes is a hallmark of altered immune status in patients with a systemic inflammatory response syndrome (SIRS). So far, the analyses were mainly performed without taking into account monocytes subpopulations. We studied this modification on CD14HIGH and CD14LOW monocytes of 20 SIRS patients undergoing abdominal aortic surgery (AAS), 20 patients undergoing carotid artery surgery (CAS), and 9 healthy controls, and we investigated mediators and intracellular molecules that may be involved in this process. HLA-DR on CD14HIGH monocytes started to decrease during surgery, after blood reperfusion, and was further reduced post-surgery. In contrast, HLA-DR expression on CD14LOW cells only decreased after surgery, and to a lesser extent than on CD14HIGH monocytes. Negative correlations were found between the reduction of HLA-DR expression and the change in cortisol levels for both subpopulations, whereas a negative correlation between interleukin-10 (IL-10) levels and HLA-DR modulation was only observed for CD14HIGH cells. In accordance with these ex vivo results, HLA-DR on CD14HIGH and CD14LOW monocytes of healthy donors was reduced following incubation with hydrocortisone, whereas IL-10 only acted on CD14HIGH subpopulation. Furthermore, flow cytometry revealed that the expression of IL-10 receptor was higher on CD14HIGH versus CD14LOW monocytes. In addition, hydrocortisone, and to a lesser extent IL-10, reversed the up-regulation of HLA-DR induced by bacterial products. Finally, membrane-associated RING-CH-1 protein (MARCH1) mRNA, a negative regulator of MHC class II, was up-regulated in monocytes of AAS patients on Day 1 post-surgery, and in those of healthy subjects exposed to hydrocortisone. This study reveals that HLA-DR expression is modulated differently on CD14HIGH (classical) versus CD14LOW (inflammatory) monocytes after systemic inflammation.
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