MEGAKARYOCYTES USE PODOSOME-LIKE PROTRUSIONS FOR TRANSCELLULAR PASSAGE THROUGH ENDOTHELIAL CELLS

Orateur : Anita ECKLY (EFS, Strasbourg)

Platelets derive from megakaryocytes (MK), their precursors located in the bone marrow (BM). How MK interact with endothelial cells (EC) in the BM to cross the sinusoids and deliver platelets into the circulation remains unclear. Here we investigated the cellular interactions between MK and sinusoidal EC by using in situ electron and fluorescence microscopy analyses of mouse BM. We identified four types of MK/EC interaction : flat contacts, short MK extensions, MK protrusions penetrating deeply into the endothelium, and transendothelial MK processes. The MK protrusions resulted in endothelial squeezing and fusion of the plasma membranes, leading to the formation of EC transendothelial pores. The protrusions were composed of F-actin bundles lying perpendicular to the endothelium. This F-actin organization together with the size, finger-like morphology and the protrusive properties of these MK structures suggested that they were similar to podosomes described in other cells. To confirm the podosome-like nature of MK protrusions, we studied the interactions between MK and EC in mice inactivated for myosin IIA and Arp2/3. While Arp2/3-/- mice almost completely lacked protrusions, Myh9-/- mice exhibited smaller ones, indicating that Arp2/3 is essential for the formation of MK protrusions and myosin IIA for their structural organization. Altogether, this study strongly suggest that MK use podosome-like protrusions to pass directly through the bodies of individual EC, which enables their cytoplasmic processes to reach the bloodstream and deliver platelets into the circulation.

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