The Lung Is Not a Primary Site of Platelet Biogenesis

Whether the lung is a primary site of platelet (PLT) production is still disputed. To address this question, PLT parameters in blood before and after pulmonary circulation in humans, rats, and rabbits were assessed by automatic hematology analyzers; bone marrow and pulmonary megakaryocytes in humans, mice, rats, and rabbits were evaluated by immunohistochemical staining; and pulmonary megakaryocytes in humans were analyzed by single-cell RNA sequencing. We found that the mean number of PLTs in rats was nearly threefold greater than that in rabbits and humans. The PLT distribution width after pulmonary circulation in humans, rats, and rabbits was consistently less than that before pulmonary circulation. However, except for the PLT population in the left atrium of rats was significantly greater than that in the right ventricle (n=20), the PLT populations between the left and right atria of rats (n=19), rabbits (n=19), and humans (n=24), between the left atrium and right ventricle of rabbits (n=19), and between the inferior vena cava and radial artery of humans (n=93) had no differences. Moreover, megakaryocytes in the lungs of mice, rats, rabbits, and humans were mononuclear, were mainly located perivascularly, and accounted for approximately 3-5 ‰. Their numbers were significantly lower, and their sizes were smaller than those of bone marrow. Conclusively, the lung can produce PLTs, but it is not a primary site of PLT biogenesis. The capability of pulmonary PLT generation differs among species; at least in rats, it is greater than that in rabbits and humans.