biostudies-literatureBoulaftali YNHLBI NIH HHSNCI NIH HHS908-16https://www.ebi.ac.uk/biostudies/studies/S-EPMC3561801biostudies-literatureUnknown123(2)Platelets play a critical role in maintaining vascular integrity during inflammation, but little is known about the underlying molecular mechanisms. Here we report that platelet immunoreceptor tyrosine activation motif (ITAM) signaling, but not GPCR signaling, is critical for the prevention of inflammation-induced hemorrhage. To generate mice with partial or complete defects in these signaling pathways, we developed a protocol for adoptive transfer of genetically and/or chemically inhibited platelets into thrombocytopenic (TP) mice. Unexpectedly, platelets with impaired GPCR signaling, a crucial component of platelet plug formation and hemostasis, were indistinguishable from WT platelets in their ability to prevent hemorrhage at sites of inflammation. In contrast, inhibition of GPVI or genThe Journal of clinical investigationPlatelet ITAM signaling is critical for vascular integrity in inflammation.PMC3561801R01 HL050545R01 HL094594F32 HL099175T32 HL007149HL50545R01 HL072798HL006350HL106009P30 CA016086HL072798P01 HL006350R01 HL067311R01 HL103432R01 HL106009Boulaftali YStolla MOwens APHess PRWare JKahn MLBergmeier WMackman NGetz TMCholka AfalsePlatelet ITAM signaling is critical for vascular integrity in inflammation.Platelets play a critical role in maintaining vascular integrity during inflammation, but little is known about the underlying molecular mechanisms. Here we report that platelet immunoreceptor tyrosine activation motif (ITAM) signaling, but not GPCR signaling, is critical for the prevention of inflammation-induced hemorrhage. To generate mice with partial or complete defects in these signaling pathways, we developed a protocol for adoptive transfer of genetically and/or chemically inhibited platelets into thrombocytopenic (TP) mice. Unexpectedly, platelets with impaired GPCR signaling, a crucial component of platelet plug formation and hemostasis, were indistinguishable from WT platelets in their ability to prevent hemorrhage at sites of inflammation. In contrast, inhibition of GPVI or gen2013-01-01T00:00:00Z2013 Feb2025-04-19T12:18:09.384Z2019-03-27T01:04:11ZS-EPMC35618012334873810.1172/JCI6515410.1172/jci65154