Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
Kellie R Machlus
Department of Medicine, Hematology Division, Brigham and Women's Hospital and Harvard Medical School, Boston, United States
Marta Martínez-Bonet
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
Pui Y Lee
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States; Department of Medicine, Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, United States
Alexandra Wactor
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
Nathan Nelson-Maney
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
Allyn Morris
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
Li Guo
Program in Molecular Medicine and Department of Internal Medicine, University of Utah, Salt Lake City, United States
Andrew Weyrich
Program in Molecular Medicine and Department of Internal Medicine, University of Utah, Salt Lake City, United States
Martha Sola-Visner
Department of Neonatology, Boston Children’s Hospital, Harvard Medical School, Boston, United States
Eric Boilard
Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l’Université Laval, Québec, Canada
Joseph E Italiano
Department of Medicine, Hematology Division, Brigham and Women's Hospital and Harvard Medical School, Boston, United States; Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, United States
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States; Department of Medicine, Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, United States
Bone marrow megakaryocytes engulf neutrophils in a phenomenon termed emperipolesis. We show here that emperipolesis is a dynamic process mediated actively by both lineages, in part through the β2-integrin/ICAM-1/ezrin pathway. Tethered neutrophils enter in membrane-bound vesicles before penetrating into the megakaryocyte cytoplasm. Intracytoplasmic neutrophils develop membrane contiguity with the demarcation membrane system, thereby transferring membrane to the megakaryocyte and to daughter platelets. This phenomenon occurs in otherwise unmanipulated murine marrow in vivo, resulting in circulating platelets that bear membrane from non-megakaryocytic hematopoietic donors. Transit through megakaryocytes can be completed as rapidly as minutes, after which neutrophils egress intact. Emperipolesis is amplified in models of murine inflammation associated with platelet overproduction, contributing to platelet production in vitro and in vivo. These findings identify emperipolesis as a new cell-in-cell interaction that enables neutrophils and potentially other cells passing through the megakaryocyte cytoplasm to modulate the production and membrane content of platelets.
