Cutting edge: Leukotriene C4 activates mouse platelets in plasma exclusively through the type 2 cysteinyl leukotriene receptor.
Cutting edge: Leukotriene C4 activates mouse platelets in plasma exclusively through the type 2 cysteinyl leukotriene receptor.
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DOI：
10.4049/jimmunol.1302187
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发表时间：
2013-12-15
期刊：
影响因子：
--
通讯作者：
Boyce JA
中科院分区：
文献类型：
--
作者：
Cummings HE;Liu T;Feng C;Laidlaw TM;Conley PB;Kanaoka Y;Boyce JA
白三烯（LT）C4及其细胞外代谢产物LTD 4和LTE 4介导气道炎症。它们通过具有重叠配体偏好的三种特异性受体（CysLT 1 R、CysLT 2 R和GPR 99）进行信号传导。在这里，我们证明了LTC 4，而不是LTD 4或LTE 4，激活小鼠血小板只通过CysLT 2 R。血小板表达CysLT 1 R和CysLT 2 R蛋白。LTC 4诱导WT小鼠富血小板血浆（PRP）中血小板表面表达CD 62 P，并导致其分泌血栓素A2和CXCL 4。LTC 4对缺乏CysLT 1 R或GPR 99的小鼠的PRP完全有活性，但对CysLT 2 R-null（Cysltr 2 −/−）小鼠的PRP完全无活性。LTC 4/CysLT 2 R信号传导需要通过P2 Y12受体的自分泌ADP介导的应答。LTC 4以血小板和CysLT 2 R依赖性方式增强气道炎症。因此，血小板上的CysLT 2 R以意想不到的选择性识别LTC 4。新生LTC 4可以在与粒细胞的突触处激活血小板，然后转化为LTD 4，促进介质产生和促进炎症的白细胞/血小板复合物的形成。
Leukotriene (LT)C4 and its extracellular metabolites, LTD4 and LTE4, mediate airway inflammation. They signal through three specific receptors (CysLT1R, CysLT2R, and GPR99) with overlapping ligand preferences. Here we demonstrate that LTC4, but not LTD4 or LTE4, activates mouse platelets exclusively through CysLT2R. Platelets expressed CysLT1R and CysLT2R proteins. LTC4 induced surface expression of CD62P by WT mouse platelets in platelet-rich plasma (PRP) and caused their secretion of thromboxane A2 and CXCL4. LTC4 was fully active on PRP from mice lacking either CysLT1R or GPR99, but completely inactive on PRP from CysLT2R-null (Cysltr2−/−) mice. LTC4/CysLT2R signaling required an autocrine ADP-mediated response through P2Y12 receptors. LTC4 potentiated airway inflammation in a platelet- and CysLT2R-dependent manner. Thus, CysLT2R on platelets recognizes LTC4 with unexpected selectivity. Nascent LTC4 may activate platelets at a synapse with granulocytes before it is converted to LTD4, promoting mediator generation and the formation of leukocyte/platelet complexes that facilitate inflammation.
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DOI：
10.4049/jimmunol.1201865
发表时间：
2012-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Barrett NA;Fernandez JM;Maekawa A;Xing W;Li L;Parsons MW;Austen KF;Kanaoka Y
通讯作者：
Kanaoka Y
DOI：
10.1164/rccm.201109-1712oc
发表时间：
2012-03-01
影响因子：
24.7
作者：
Johansson, Mats W.;Han, Shih-Tsung;Mosher, Deane F.
通讯作者：
Mosher, Deane F.
影响因子：
6.7
作者：
Momi, S;Pitchford, SC;Gresele, P
通讯作者：
Gresele, P
DOI：
10.1164/ajrccm.164.8.2102033
发表时间：
2001-10-15
影响因子：
24.7
作者：
Gauvreau, GM;Parameswaran, KN;O'Byrne, PM
通讯作者：
O'Byrne, PM
影响因子：
2.8
作者：
DRAZEN, JM;ISRAEL, E
通讯作者：
ISRAEL, E