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 genetic deletion of
Yacine Boulaftali, Paul R. Hess, Todd M. Getz, Agnieszka Cholka, Moritz Stolla, Nigel Mackman, A. Phillip Owens III, Jerry Ware, Mark L. Kahn, Wolfgang Bergmeier
In vivo function of WT platelets transfused into TP hIL-4Rα/GPIbα–Tg mice.