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Innate immunity and expressions of TLRs during upper abdominal surgery

上腹部手术中先天免疫和TLRs的表达

基本信息

批准号：
14370499
负责人：
OGATA Masanori
金额：
$ 5.7万
依托单位：
University of Occupational Environmental Health(UOEH)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370499/
关键词：
Toll like receptor Innate immunit Surgical stress phagocytosis Oxygen burst Anesthesia MIF HSP-70 Toll like receptor 自然免疫エンドトキシン感受性 TNF 外科浸襲

项目摘要

We have demonstrated that surgical stress rapidly induced transient hyporesponsiveness of blood cells to endotoxin and that monocyte mCD 14 and HLA-DR expression reduced from the early period of surgery under general anesthesia. The Toll-like receptors (TLRs) are one of the most important pattern recognition receptor families TLR2 recognizes gram-positive organism-derived pathogen-associated molecular patterns and TLR4 recognized both viral components and gram-negative LPS. The aim of this study was to examine the expressions of Toll-like receptor (TLR)-2 and 4 during surgery.Materials & Methods・After obtaining approval from our committee on human research and informed consents, the blood samples were obtained from the 23 patients of upper abdominal surgery before incision (Pre-OP), at 2hr after incision (OPE2h), the end of surgery (Post-OPE) and 24hr after incision(OPE24hr).・The blood cells were incubated for 30min in the dark with a saturating concentration of fluorescein isothiocyan … More ate (FITC)-labeled monoclonal antibodies directed against TLR2, or with a saturating concentration of physoerythrin (PE)-labeled monoclonal antibodies directed against TLR4. A lysing medium was added to lyse erythrocyte, and after lysis was complete, the samples were fixed 0.2% paraformaldehyde and washed twice. All samples were analyzed immediately using flow cytometry and XL software (EPIC-XL; Beckman Culter Electronics). The results were described as the mean fluorescence intensity.・Plasma levels of IL-10,MIF, HSP-7Results1. Both expression of TLR2 and TLR4 significantly decreased from OPE2h and recovered slightly at OPE24h.2. Both of plasma IL-10 and cortisol increased significantly from OPE2h.3. Plasma MIF increased significantly from 2h after incision. Plasma HSP-70 increased significantly at the end of an operation.Conclusions1) Both expressions of TLR2 and TLR4 significantly decreased at the early period of an operation.2) Anti-inflammatory mediators such as IL-10 and cortisol may cause the decrease of TLR expressions.3) In contrast, HSP-70 and MIF may restore the decrease of TLR expressions.4) It should be noted that the impairment of host-defense mechanisms occurs at the early period of an operation. Less

我们已经证明，手术应激迅速诱导血细胞对内毒素的短暂低反应性，并且在全身麻醉下，单核细胞mCD 14和HLA-DR表达从手术早期开始减少。Toll样受体（TLR）是最重要的模式识别受体家族之一，TLR 2识别革兰氏阳性菌源性病原体相关分子模式，TLR 4识别病毒成分和革兰氏阴性菌LPS。本研究的目的是检测Toll样受体（TLR）-2和4在手术过程中的表达。材料与方法·在获得我们的人类研究委员会批准和知情同意后，从23例上腹部手术患者的切口前（Pre-OP）、切口后2 h（OPE 2 h）、手术结束时（Post-OPE）和切口后24小时（OPE 24小时）。将血细胞在黑暗中与饱和浓度的异硫氰酸荧光素孵育30分钟 ...更多信息用饱和浓度的藻红蛋白（PE）标记的抗TLR 4的单克隆抗体，或用饱和浓度的藻红蛋白（PE）标记的抗TLR 2的单克隆抗体。加入裂解液裂解红细胞，裂解完成后，用0.2%多聚甲醛固定，洗涤两次。立即使用流式细胞术和XL软件（EPIC-XL; Beckman卡尔特电子公司）分析所有样品。结果以平均荧光强度表示。·血浆IL-10、MIF、HSP-7水平TLR 2和TLR 4的表达均从OPE 2 h开始显著降低，在OPE 24 h略有恢复。血浆IL-10和皮质醇均从OPE 2 h开始显著升高。血浆MIF从切皮后2 h开始明显升高。结论1）TLR 2和TLR 4在手术早期表达均明显下降; 2）抗炎介质IL-10和皮质醇可能是导致TLR表达下降的原因。HSP-70和MIF可恢复TLR表达的下降。4）应注意的是，宿主防御机制的受损发生在手术的早期。少