Platelet Biogenesis in the Lung Circulation

Abstract

Megakaryocytes are normal cellular components of the blood returning to the heart and entering the lungs, and historical data has pointed to a role of the lungs in platelet production. Recent studies using intravital microscopy have demonstrated that platelet release occurs in the lung from bone marrow megakaryocytes that embolize into the lung circulation.

Keywords: lung; megakaryocytes; platelets; thrombopoiesis.

FIGURE 1.

Platelet production in the lung circulation and its regulation Platelet production in the lung circulation is the result of proplatelets and megakaryocytes released in spleen and bone marrow sinusoids. We can thus differentiate two levels of regulation: 1) proplatelet release and megakaryocyte egress from spleen and bone marrow, and 2) platelet shedding in the lung vasculature. 1: proplatelet release and megakaryocyte egress depend on megakaryocyte maturation (driven by thrompopoietin) and translocation to the perivascular environment (driven by SDF-1 and FGF-4). Sensing the microenvironment (collagen-rich osteoblastic niche or endothelial cells) regulates proplatelet formation, and transendothelial proplatelet migration and proplatelet shedding into the circulation is regulated by a S1P gradient. Thin proplatelets, large protrusions, and whole megakaryocytes can be released into the circulation. The different types of fragments or cells released is dependent on platelet demand, inflammatory signals, or site of origin. 2: in the lung vasculature, megakaryocytes and cytoplasmic fragments are trapped in vascular bifurcations where shear stress and turbulence must be ideal for final platelet shedding. The importance of other signals, such as the interaction with pulmonary endothelial cells, needs to be further elucidated.

FIGURE 2.

Circulating and resident megakaryocytes in the lung Two types of megakaryoctyes are found in the lung, differing in their location, origin, maturation, shape, and role in thrombopoiesis. Circulating megakaryocytes arrest at vascular bifurcations. They are of extrapulmonary origin, likely released in the bone marrow and spleen sinusoids. These megakaryocytes produce several pseudopodial extensions and release individual platelets in the lung circulation. Resident megakaryocytes are found in the lung interstitium. Their origin is unknown, and they present a more immature profile. These cells are sessile, and transcriptomic data point to a potential role in lung immunity. Further studies should determine their exact function and their capacity to migrate and produce platelets.