Complement links platelets to innate immunity

The complement system is a versatile part of our immune system. Various intersection points of complement with other cells and molecules of the immune response are well described. Platelets are classically conceived as cells of hemostasis. In recent years, however, several functions of platelets "beyond thrombosis" were discovered. This review depicts the crosstalk of platelets with components of the immune system in the context of thrombo-inflammation. In particular, the various ways, in which platelets interact with the complement system, are illustrated. Platelets cannot only aggravate vascular inflammation and cardiovascular diseases, but they also contribute to organ remodeling and tissue homeostasis. Here, we portray the role of complement factors associated with platelet activation in tissue remodeling. Importantly, the clinical relevance of this platelet-complement crosstalk is addressed. A focus lies on thrombo-inflammatory disorders, other diseases with thromboembolic mechanisms or complications, but also autoimmune diseases. Finally, we draw attention to the growing body of evidence on the role of complement-platelet crosstalk in cardiovascular diseases. For future clinical, translational and basic science approaches, this crosstalk may prove a fruitful area of research in order to procure novel therapeutic and diagnostic targets in cardiovascular medicine and previously less addressed diseases featuring a platelet-complement axis.