Necessity of Thromboxane A2 for Initiation of Platelet-Mediated Contact Sensitivity: Dual Activation of Platelets and Vascular Endothelial Cells1
Necessity of Thromboxane A2 for Initiation of Platelet-Mediated Contact Sensitivity: Dual Activation of Platelets and Vascular Endothelial Cells1
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血栓素 A2 启动血小板介导的接触敏感性的必要性：血小板和血管内皮细胞的双重激活1
作者：
Motoki Mitsuhashi;A. Tanaka;C. Fujisawa;K. Kawamoto;A. Itakura;M. Takaku;Takasi Hironaka;S. Sawada;H. Matsuda
为了研究血小板源性血栓素A2（TXA 2）在引发Ag特异性接触敏感性（CS）中的关键作用，提供了一种使用遗传性肥大细胞缺陷的W/Wv小鼠的血小板依赖性CS模型。BAYu 3405，一种TXA 2受体拮抗剂，在体内治疗，显着抑制CS反应的剂量依赖性方式。当BAYu 3405在早期启动阶段之前给药时，这种抑制作用发生，表明TXA 2可能是血小板介导的CS反应的有效启动剂。当血小板在体外用BAYu 3405预处理时，血小板聚集以及5-羟色胺释放（其能够诱导早期反应，允许由于血管内皮细胞的直接活化而局部募集CS效应T细胞）被抑制。另外，U46619，TXA 2激动剂，或血小板和凝血酶的混合物增强ICAM-1和VCAM-1在分离的小鼠主动脉内皮细胞上的表达，这是完全取消预处理BAYu 3405。此外，将U46619皮内注射到血小板耗尽小鼠的耳中导致CS反应，在血管内皮上具有显著的ICAM-1和VCAM-1表达。这些结果表明，从血小板产生的TXA 2与Ag激活可能介导的CS反应的启动，通过诱导5-羟色胺从血小板和随后的聚集和上调ICAM-1和VCAM-1的表达血管内皮细胞上的释放。
To investigate the crucial role of platelet-derived thromboxane A2 (TXA2) in initiating Ag-specific contact sensitivity (CS), a platelet-dependent CS model using genetically mast cell-deficient W/Wv mice, was provided. In vivo treatment with BAYu3405, a TXA2 receptor antagonist, markedly suppressed CS responses in a dose-dependent manner. This inhibitory effect occurred when BAYu3405 was administered before an early initiating phase, suggesting that TXA2 may be a potent initiator of platelet-mediated CS responses. When platelets were pretreated with BAYu3405 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. The addition of U46619, a TXA2 agonist, or a 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 pretreatment with BAYu3405. Furthermore, intradermal injection of U46619 into the ear of platelet-depleted mice led to CS responses with marked expression of ICAM-1 and VCAM-1 on the vascular endothelium. These findings suggest that TXA2 generated from platelets activated with Ag may mediate initiation of CS responses through inducing serotonin release from platelets and the subsequent aggregation and up-regulated expression of ICAM-1 and VCAM-1 on vascular endothelial cells.
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IgE 蛋白与人血小板的体外结合。
DOI：
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发表时间：
1986
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cines,DB;vanderKeyl,H;Levinson,AI
通讯作者：
Levinson,AI
人血小板可以通过 IgE 抗体介导的局部血清素释放来启动 T 细胞依赖性接触敏感性。
DOI：
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发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Matsuda,H;Ushio,H;Geba,GP;Askenase,PW
通讯作者：
Askenase,PW
通过抗原特异性非 IgE 因子或 IgE 抗体募集 T 细胞亚群的迟发型超敏反应：与哮喘、自身免疫以及对肿瘤和寄生虫的免疫反应的相关性。
影响因子：
--
作者：
Askenase,PW
通讯作者：
Askenase,PW
选择性剪接在人内皮血栓素 A2 受体中产生不同的细胞质尾部。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Raychowdhury,MK;Yukawa,M;Collins,LJ;McGrail,SH;Kent,KC;Ware,JA
通讯作者：
Ware,JA
肥大细胞缺陷小鼠的迟发型超敏反应：依赖于血小板来表达接触敏感性。
DOI：
--
发表时间：
1996
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Geba,GP;Ptak,W;Anderson,GM;Paliwal,V;Ratzlaff,RE;Levin,J;Askenase,PW
通讯作者：
Askenase,PW