Cutting edge: Leukotriene C4 activates mouse platelets in plasma exclusively through the type 2 cysteinyl leukotriene receptor

HE Cummings, T Liu, C Feng, TM Laidlaw… - The Journal of …, 2013 - journals.aai.org
HE Cummings, T Liu, C Feng, TM Laidlaw, PB Conley, Y Kanaoka, JA Boyce
The Journal of Immunology, 2013journals.aai.org
Abstract Leukotriene C 4 (LTC 4) and its extracellular metabolites, LTD 4 and LTE 4,
mediate airway inflammation. They signal through three specific receptors (type 1 cys-LT
receptor [CysLT 1 R], CysLT 2 R, and GPR99) with overlapping ligand preferences. In this
article, we demonstrate that LTC 4, but not LTD 4 or LTE 4, activates mouse platelets
exclusively through CysLT 2 R. Platelets expressed CysLT 1 R and CysLT 2 R proteins. LTC
4 induced surface expression of CD62P by wild-type mouse platelets in platelet-rich plasma …
Abstract
Leukotriene C 4 (LTC 4) and its extracellular metabolites, LTD 4 and LTE 4, mediate airway inflammation. They signal through three specific receptors (type 1 cys-LT receptor [CysLT 1 R], CysLT 2 R, and GPR99) with overlapping ligand preferences. In this article, we demonstrate that LTC 4, but not LTD 4 or LTE 4, activates mouse platelets exclusively through CysLT 2 R. Platelets expressed CysLT 1 R and CysLT 2 R proteins. LTC 4 induced surface expression of CD62P by wild-type mouse platelets in platelet-rich plasma (PRP) and caused their secretion of thromboxane A 2 and CXCL4. LTC 4 was fully active on PRP from mice lacking either CysLT 1 R or GPR99, but completely inactive on PRP from CysLT 2 R-null (Cysltr2−/−) mice. LTC 4/CysLT 2 R signaling required an autocrine ADP-mediated response through P2Y 12 receptors. LTC 4 potentiated airway inflammation in a platelet-and CysLT 2 R-dependent manner. Thus, CysLT 2 R on platelets recognizes LTC 4 with unexpected selectivity. Nascent LTC 4 may activate platelets at a synapse with granulocytes before it is converted to LTD 4, promoting mediator generation and the formation of leukocyte–platelet complexes that facilitate inflammation.
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