Platelets contribute to allograft rejection through glutamate receptor signaling.
Platelets contribute to allograft rejection through glutamate receptor signaling.
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血小板通过谷氨酸受体信号传导有助于同种异体移植排斥。
DOI：
10.4049/jimmunol.1000929
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Morrell CN
中科院分区：
文献类型：
--
作者：
Swaim AF;Field DJ;Fox-Talbot K;Baldwin WM 3rd;Morrell CN
血小板募集白细胞并介导白细胞和内皮细胞之间的相互作用。长期以来，血小板一直被描述为移植排斥的标志物，但血小板对移植排斥的贡献尚未得到严格研究。我们现在证明，在 T 细胞引发同种异体移植排斥反应后，血小板有助于 T 细胞募集、增加血浆炎症介质并加速 T 细胞介导的皮肤移植排斥反应。我们实验室之前的工作表明，血小板在激活时会分泌谷氨酸，然后通过血小板表达的离子型谷氨酸受体发出信号，诱导血小板血栓素产生。因此，谷氨酸受体拮抗剂代表了血小板加速炎症的新型抑制剂。我们发现接受皮肤移植的小鼠的血浆谷氨酸含量增加，并且用谷氨酸受体拮抗剂治疗的小鼠改善了移植物的存活率并降低了血浆血栓素、血小板因子 4 (PF4/CXCL4) 和 IFNγ。总而言之，我们的工作现在表明，在 T 细胞引发皮肤移植排斥之后，血小板有助于进一步的 T 细胞募集，并且通过减弱谷氨酸介导的血小板活化，可以提高移植物的存活率。
Platelets recruit leukocytes and mediate interactions between leukocytes and endothelial cells. Platelets have been long described as markers of transplant rejection, but the contribution of platelets to transplant rejection has not been critically examined. We now demonstrate that following T-cell initiation of allograft rejection platelets contribute to T-cell recruitment, increased plasma inflammatory mediators, and accelerate T-cell meditated skin graft rejection. Prior work from our lab has shown that platelets secrete glutamate when activated, which then induces platelet thromboxane production by signaling through platelet expressed ionotropic glutamate receptors. Glutamate receptor antagonists therefore represent novel inhibitors of platelet accelerated inflammation. We have found that plasma glutamate is increased in mice that receive skin grafts and that mice treated with glutamate receptor antagonists have improved graft survival and decreased plasma thromboxane, platelet factor 4 (PF4/CXCL4) and IFNγ. Taken together, our work now demonstrates that subsequent to T-cell initiation of skin graft rejection, platelets contribute to further T-cell recruitment and that by blunting glutamate mediated platelet activation, graft survival is improved.
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影响因子：
30.3
作者：
Srivastava, Kalyan;Cockburn, Ian A;Swaim, AnneMarie;Thompson, Laura E;Tripathi, Abhai;Fletcher, Craig A;Shirk, Erin M;Sun, Henry;Kowalska, M Anna;Fox-Talbot, Karen;Sullivan, David;Zavala, Fidel;Morrell, Craig N
通讯作者：
Morrell, Craig N
影响因子：
8.8
作者：
Murata, K.;Fox-Talbot, K.;Wasowska, B. A.
通讯作者：
Wasowska, B. A.
影响因子：
6.1
作者：
Narumiya, S
通讯作者：
Narumiya, S
影响因子：
6.2
作者：
DEWAAL, RMW;BOGMAN, MJJT;KOENE, RAP
通讯作者：
KOENE, RAP
影响因子：
4.4
作者：
Nakashima, S;Qian, ZP;Baldwin, WM
通讯作者：
Baldwin, WM