Platelets and inflammatory disorders of connective tissue

The circulating blood platelet as a participant in inflammatory pathways has been the focus of intense investigation and the topic of several reviews and other chapters in this book (Franco et al. Blood. 126:582-588, 2015). Inflammation underlies the pathophysiologic response in many diseases, and therefore defining the role of the platelet in inflammatory responses is paramount to understanding the molecular basis of the disease process (Leslie. Science 328(5978):562-564, 2010). In this chapter, we focus on the historical background describing the role of platelets in connective tissue inflammation, with emphasis on studies linking platelets and rheumatoid arthritis. A link between platelets and the inflammatory response starts with an appreciation for platelets being a specific cellular entity restricted to higher mammals. Lower vertebrates, such as fish and birds, do not have platelets, but instead have a dual-functioning cell, the thrombocyte, that has both immune and hemostatic properties (see Momi and Wiwanitkit 2017). Thus, the divergence of thrombocyte function to multiple cell types, such as neutrophils, monocytes, and platelets, might be expected to result in functional overlap with some similar properties retained by each individual cell type in higher species. The participation of platelets in inflammation needs careful consideration given the widespread use of antithrombotic agents for prevention of cardiovascular events. Understanding the molecular basis of the platelet/inflammatory axis will also ensure the best practice decisions will be made for the treatment of cardiovascular disease and additional inflammatory conditions.