Megakaryocyte emperipolesis: a new frontier in cell-in-cell interaction

Abstract

Histology of bone marrow routinely identifies megakaryocytes that enclose neutrophils and other hematopoietic cells, a phenomenon termed emperipolesis. Preserved across mammalian species and enhanced with systemic inflammation and platelet demand, the nature and significance of emperipolesis remain largely unexplored. Recent advances demonstrate that emperipolesis is in fact a distinct form of cell-in-cell interaction. Following integrin-mediated attachment, megakaryocytes and neutrophils both actively drive entry via cytoskeletal rearrangement. Neutrophils enter a vacuole termed the emperisome which then releases them directly into the megakaryocyte cytoplasm. From this surprising location, neutrophils fuse with the demarcation membrane system to pass membrane to circulating platelets, enhancing the efficiency of thrombocytogenesis. Neutrophils then egress intact, carrying megakaryocyte membrane and potentially other cell components along with them. In this review, we summarize what is known about this intriguing cell-in-cell interaction and discuss potential roles for emperipolesis in megakaryocyte, platelet and neutrophil biology.

Keywords: Emperipolesis; megakaryocyte; neutrophil.

Figure 1:

Cell-in-cell interactions

Figure 2:. Steps of megakaryocyte emperipolesis.

(1) ICAM-1/ezrin cluster on the MK surface upon neutrophil attachment to facilitate interaction with neutrophil β2 integrins. (2) Neutrophils enter into MK vacuole (“emperisome”) in an actin-dependent manner. (3) The emperisome contracts around the neutrophil to enable close contact between neutrophil and emperisome membranes. (4) Neutrophils exit the emperisome and translocate to the DMS, where they transfer membrane and proteins to MKs and platelets. (5) Egress of viable neutrophil from MK (model adapted from (21)).