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Immunological Analysis and Regulation of Platelet Activation in Delayed-Type Hypersensitivity

迟发型超敏反应中血小板激活的免疫学分析和调节

基本信息

批准号：
09460137
负责人：
MATSUDA Hiroshi
金额：
$ 9.98万
依托单位：
Tokyo University of Agriculture & Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09460137/
关键词：
contact sensitivity platelets mouse model thromboxane serotonin adhesion molecules endothelial cells nerve growth factor T細胞インテグリンセレクチン IgE lgE

项目摘要

Platelets express specific receptors such as IgE and adhesion molecules and activation mechanisms through them have been discussed. In the present research project, we investigated the possible involvement of platelets in the process of delayed-type hypersensitivity, such as contact sensitivity and atopic dermatitis. The obtained resulted are follows:1) In vivo treatment with BA Yu3405, a (thromboxane AィイD22ィエD2) TXAィイD22ィエD2 receptor antagonist, markedly suppressed CS responses in genetically mast cell-deficient W/WィイD1vィエD1 mice and the inhibitory effect was occurred when BA Yu3405 was administered before an early initiating phase, suggesting that TXAィイD22ィエD2 may be a potent initiator of platelet-mediated CS responses.2) When platelets were pretreated with BA Yu3405 in vitro, platelet aggregation as well as serotonin release, which is able to induce the early phase response allowing local recruitment of CS effector T cells due to direct activation of vascular endothelial cells, was inhibited.3) Furthermore, the addition of U46619, a TXAィイD22ィエD2 agonist, or mixture of platelets and thrombin enhanced expression of both ICAM-1 and VCAM-1 on isolated mouse aortic endothelial cells, which was completely abolished by the pretreatment with BA Yu3405. These findings suggest that TXAィイD22ィエD2 generated from platelets activated with Ag may mediate initiation of CS responses through leading serotonin release from platelets and the subsequent aggregation and upregulating expression of ICAM-1 and VCAM-1 on the vascular endothelial cells.4) Lysophosphatidylserine expressed on the membrane of the activated platelets was able to mediate nerve growth factor-dependent release of serotonin form rat peritoneal mast cells. This lysophosphatidylserine-mediated mast cell activation was demonstrated in vivo, providing novel evidence of an inflammatory cascade in allergic responses.

血小板表达特异性受体，如IgE和黏附分子，并对其激活机制进行了讨论。在目前的研究项目中，我们调查了血小板在迟发性超敏反应过程中的可能参与，如接触敏感症和特应性皮炎。结果表明：(1)血栓素A-ィイ-D22-ィエ-D2受体拮抗剂BA-Yu3405可显著抑制W/W-ィエD1v-ィエ-d1小鼠的CS反应，且BA Yu3405可抑制ィイ-D1v-ィエ-D1小鼠的CS反应，提示TXA-ィイ-D22-ィエ-D2可能是血小板介导的CS反应的有效起始者。3)此外，加入TXAィイD22ィエD2激动剂U46619或血小板与凝血酶的混合物可促进小鼠主动脉内皮细胞上细胞间黏附分子-1和血管细胞间黏附分子-1的表达，而BA Yu3405可完全取消这一作用。这些结果表明，由抗原激活的血小板产生的TXAィイD22ィエD2可能通过引导血小板释放5-羟色胺以及随后血管内皮细胞上细胞间黏附分子-1和血管细胞间黏附分子-1的聚集和上调来介导CS反应的启动。4)活化的血小板膜上表达的溶血磷脂酰丝氨酸能够介导神经生长因子依赖的大鼠腹膜肥大细胞释放5-羟色胺。这种溶血磷脂酰丝氨酸介导的肥大细胞激活在体内被证实，为过敏反应中的炎症级联反应提供了新的证据。