The physical and cellular conditions of the human pulmonary circulation enable thrombopoiesis

• Published in: Experimental hematology 2018-07, Vol.63, p.22-27.e3
• Main Authors: Ouzegdouh, Yasmine, Capron, Claude, Bauer, Thomas, Puymirat, Etienne, Diehl, Jean-Luc, Martin, John F., Cramer-Bordé, Elisabeth
• Format: Article
• Language: English
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2018.04.001

•Human mature megakaryocytes (MKs) may enter the pulmonary circulation.•The endothelial microenvironment favors platelet formation.•Shear stress and immobilized glycoprotein Ib (GpIb) ligand are determinant for platelet production.•Polyploid MKs have the potential to change ploidy under flow conditions.•This is a newly recognized environment affecting platelet production. Animal evidence that platelet production occurs in the lungs is growing. We have investigated whether there is evidence to support pulmonary platelet production from studies using human conditions. We documented the presence of megakaryocytes (MKs) in the human pulmonary circulation and analyzed the role of the vascular microenvironment on MK function. Our results suggest that the endothelial microenvironment favors platelet formation and that von Willebrand factor combined with appropriate physical forces in flowing blood are determinant for platelet release. We also demonstrate that MKs have the potential to change ploidy as they circulate. These findings demonstrate a new pathophysiological environment affecting platelet production and provide new targets for therapeutic intervention.