Megakaryocytes in the lung: History and future perspectives

A state of the art lecture titled "Megakaryocytes in the Lung" was presented at the London International Society on Thrombosis and Haemostasis congress in 2022. This lecture highlighted that although most medical teaching presents platelets as bone marrow megakaryocyte-derived cellular mediators of thrombosis, platelets are also a critical part of the immune system with direct roles in responses to sterile tissue injury and pathogens. Bone marrow megakaryocytes differentiate from hematopoietic stem cells and package platelets with immune molecules. Activated platelets, therefore, initiate or accelerate the progression of vascular inflammatory pathologies, as well as being regulators of immune responses to infectious agents. Platelets are now known to have mechanistic roles in immune responses to disease processes, such as heart transplant rejection, myocardial infarction, aortic aneurysm, peripheral vascular disease, and infections. From these studies comes the concept that megakaryocytes are immune cell progenitors and recent emerging information highlights that megakaryocytes may themselves be immune cells. Despite megakaryocytes being described in the lung for >100 years, lung megakaryocytes have only recently been shown to be platelet producing and lung megakaryocytes are immune-differentiated in both phenotype and function. What is still not known is the origin of lung megakaryocytes and roles of lung megakaryocytes in health and disease. This review will discuss the long history of lung megakaryocytes in the literature and potential models for megakaryocyte origins and immune functions. Finally, we summarize relevant new data related to this topic that was presented during the 2022 International Society on Thrombosis and Haemostasis Congress.