Molecular Analysis of Platelet-Immunocyte Interaction

血小板-免疫细胞相互作用的分子分析

基本信息

批准号：
03671045
负责人：
TSUJI Tsutomu
金额：
$ 1.28万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03671045/
关键词：
Selectin Adhesion molecule Platelet Leukocyte Oxygen radical Inflammation Carbohydrate chain 細胞接着サイトカイン

项目摘要

We have examined the effect of inflammatory cytokines on the platelet activation. IL-beta and IFN-gamma were found to enhance the adhesion of thrombin-treated platelets to moncytic leukemia cells(U937),when the adhesion was assayed by platelet-mediated cell agglutination. The agglutination was inhibited by a monoclonal anti-P-selectin antibody or EDTA,suggesting that the enhanced platelet adhesion to the leukemic cells was mediated by P-selectin. In addition,these cytokines also increased the release of 5-HT from platelets in the presence of a low concentration of thrombin. These data suggest that platelet functions are regulated by the cytokines and that activated platelets participate in inflammatory process. We next examined the possibility that leukocytes are functionally modified by their adhesion to activated platelets. We used human peripheral blood monocytes and neutrophils and measured superoxide anion generation by these cells cultured with platelets. The levels of superoxide anion production was found to be markedly elevated when thrombin-activated platelets were used.This enhancement was not observed when cultured with resting platelets. The increase depended on incubation time and platelet concentration. The membranes prepared from activated platelets also induced superoxide anion production,but the culture supernatant of activated platelets did not. The enhanced superoxide anion production was inhibited by anti-P-selectin antibody,anti-sialyl-Le^X antibody or a soluble recombinant P-selectin-glutathione-S-transferase(GST) fusion protein. These results indicate that the adhesion of activate dplatelets to the leukocytes through P-selectin was a crucial step for the activation of leukocyte function, and support the idea that activated platelets are actively involved in inflammation processes.

我们已经检查了炎性细胞因子对血小板激活的影响。当通过血小板介导的细胞凝集测定粘附时，发现IL-BETA和IFN-GAMMA可增强凝血酶处理的血小板对蒙眼白血病细胞的粘附（U937）。单克隆抗P-选择蛋白抗体或EDTA抑制了凝集，这表明增强的血小板粘附于白血病细胞是由P-蛋白介导的。此外，在低浓度的凝血酶存在下，这些细胞因子还增加了血小板5-HT的释放。这些数据表明血小板功能受细胞因子的调节，并且活化的血小板参与炎症过程。接下来，我们检查了白细胞通过激活血小板的粘附而在功能上修饰的可能性。我们使用了人类外周血单核细胞和嗜中性粒细胞，并通过这些用血小板培养的细胞测量了超氧化阴离子。当使用凝血酶激活的血小板时，发现超氧化阴离子的产生水平显着升高。当用静息血小板培养时，未观察到这种增强。增加取决于孵育时间和血小板浓度。由活化血小板制备的膜也诱导了超氧化阴离子的产生，但活化血小板的培养物上清液没有。抗P-选择蛋白抗体，抗-LEL-LE^X抗体或可溶性重组P-链甲前 - 谷胱甘肽-S-转移酶（GST）融合蛋白抑制了增强的超氧化阴离子的产生。这些结果表明，通过p-选择素激活Dplatelets对白细胞的粘附是活化白细胞功能的关键步骤，并支持激活的血小板积极参与炎症过程的想法。