Blood platelets are small, anucleate cells that play a critical role in preventing excessive bleeding at sites of injury, a process known as hemostasis. Platelet activation also triggers blood clots within the diseased circulation (thrombosis). In addition, platelets are increasingly recognized as key players in a number of major (patho)physiological processes.
Platelets are emerging as versatile effector cells involved in inflammation, innate and adapted immune response, extracellular matrix reorganization and fibrosis, maintenance of barrier and organ integrity, and host response to pathogens. Thrombotic and inflammatory events both contribute to acute organ damage in a process that we termed thrombo-inflammation. Thrombo-inflammation is best characterized in the setting of ischemic stroke: interaction of platelets and inflammatory cells (T cells) drives infarct growth despite recanalization of the previously occluded brain-feeding artery. This process is known as ischemia-reperfusion (I/R) injury. Similarly, platelets are also critically involved in I/R injury of the heart, however, the underlying molecular mechanisms appear to be different as compared to the brain. Besides their described interaction with T cells in the setting of ischemic stroke, platelets interact with monocytes in the microcirculation of the acutely ischemic myocardium. This interaction affects organ dysfunction and functional recovery. Importantly, the role of platelets in these inflammatory settings differs from their classical role in thrombus formation/hemostasis, and the molecular pathways involved remain largely elusive. We subject transgenic mice to experimental models of thrombo-inflammatory diseases to elucidate the cellular interactions underlying thrombo-inflammation.