# Modulation of neutrophil function through emperipolesis

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $220,708

## Abstract

Project Summary
For almost 50 years it has been known that neutrophils regularly appear within megakaryocytes (MKs), a
histological phenomenon termed emperipolesis. Using new tools we developed to study this process in vitro
and in vivo, we found that emperipolesis is common and increases with experimental inflammatory stress in
a murine system. Neutrophils penetrate into the MK cytoplasm, donating a fraction of their surface
membrane to platelets before emerging viable and intact. Our preliminary data show that neutrophils take
up MK-derived exosomes during emperipolesis and emerge with enhanced migratory capacity. Building on
these results, we explore the hypothesis that emperipolesis is a novel cell-in-cell interaction that modulates
the function of neutrophils.
We test this hypothesis in two independent but complementary aims. In Aim I, we examine the effect of
emperipolesis, and in particular of MK exosomes, on neutrophil effector functions, metabolism, and in vivo
migration in neutrophil-dependent K/BxN serum transfer arthritis. In Aim II, we employ whole-mount 3D
marrow imaging, 2-photon in vivo microscopy, and specific MK deletion and potentially emperipolesis
blockade to test the possibility that emperipolesis represents a quantitatively important pathway of
neutrophil egress from bone marrow in vivo, including in experimental arthritis.
Together, these studies will define a new form of cooperation between MKs and neutrophils that modulates
the ability of neutrophils to participate in health and disease. More generally, building upon our recent
identification of MKs as a source of IL-1 in arthritis, these studies continue to develop the understanding of
MKs and neutrophils as participants in systemic inflammatory disease. These “high risk, high reward”
studies of a previously overlooked biological process, widely conserved across mammalian species, will set
the stage for an extended investigation of emperipolesis as a novel cell-in-cell phenomenon.

## Key facts

- **NIH application ID:** 9877028
- **Project number:** 1R21AR076630-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Peter A Nigrovic
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $220,708
- **Award type:** 1
- **Project period:** 2020-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877028

## Citation

> US National Institutes of Health, RePORTER application 9877028, Modulation of neutrophil function through emperipolesis (1R21AR076630-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9877028. Licensed CC0.

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