A role of platelets beyond hemostasis

Abstract

It is well known that platelets play a crucial role in hemostasis, but it has recently been revealed that platelets are also necessary for organ development. The platelet activation receptor CLEC-2 activates platelets by binding to the membrane protein, podoplanin, on the surface of lymphatic endothelial cells. This results in the release of TGF-β family from activated platelets to facilitate blood/lymphatic vessel separation. TGF-β also acts on lung mesothelial cells, which leads to their differentiation into alveolar duct myofibroblasts (adMYFs) and their migration into the inside of the lung. adMYFs generate elastin, which gives elasticity to the lung. Therefore, mice deficient in either CLEC-2 or podoplanin exhibit blood/lymphatic vessel misconnection and die just after birth due to respiratory failure. It had been previously surmised that biologically active substances from cells act on neighboring cells, leading to organ development, and the role of blood cells in organ development had not been elucidated. However, it has recently been demonstrated that blood platelets contain biological active substances in their granules, which are released when and where necessary by specific interactions between platelet receptors and their ligands. Now platelets are recognized as a “biological package” that actively facilitates organ development.