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

Acknowledgements

P.C. is supported by a grant from the Arthritis National Research Foundation. P.A.N. is funded by NIH awards R01 AR065538, R01 AR073201, R01 AR075906, and P30 AR070253, by the Fundación Bechara, and by the Arbuckle Family Fund for Arthritis Research.

Conflict of interest

The authors report no conflict of interest.

Additional information

Funding

This work was supported by the Arthritis National Research Foundation [2018A000189]; National Institutes of Health [P30 AR070253,R01 AR065538, R01 AR073201, R01 AR075906]; Fundación Bechara; Arbuckle Family Fund for Arthritis Research.