# Impact of emperipolesis on platelet function

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $185,995

## Abstract

Project Summary
Megakaryocytes (MK) have been known for decades to engage in an unusual behavior termed
emperipolesis, whereby leukocytes – principally neutrophils – appear intact within the MK cytoplasm.
Emperipolesis is conserved across mammalian species. It is observed in normal marrow but becomes
particularly prevalent under conditions of increased platelet demand, but its mechanisms and functions
remain obscure. Using a new in vitro model system, we found that emperipolesis represents a high-
throughput interaction whereby neutrophils passage rapidly through MKs. During this transit, neutrophil lipid
membranes merge with the MK demarcation membrane system (DMS) and thereby contribute membrane
directly to MKs themselves and to the resulting platelets, both in vitro and in vivo. One implication of this
finding is that some circulating platelets represent hybrids, featuring both MK and neutrophil components.
The goal of this proposal is to begin to understand the physiological function of this novel biology.
Together with experienced MK/platelet collaborators Dr. Italiano and Dr. Flaumenhaft, we propose two Aims.
Aim I characterizes the process of protein transfer from neutrophils to platelets via emperipolesis, using live
cell imaging and electron microscopy, and defines the proteins transferred from neutrophils to platelets via
SILAC mass spectrometry. Aim II pursues our preliminary data that hybrid platelets are likely to exhibit
enhanced procoagulant function using in vitro assays of platelet function and in vivo imaging of platelet
accumulation in growing thrombi.
Together, these studies will initiate a novel of research into the biology of emperipolesis, illuminating a
surprising pathway of interaction between the immune and hematopoietic systems and defining a previously
unappreciated mechanism that has the potential to powerfully modulate platelet function. These “high risk,
high reward” studies of a process observed across mammalian species fits well within the mandate of FOA
PA-19-049 New Research Directions that Advance the NHLBI Strategic Vision Normal Biology to “clarify
biological processes that are both present in healthy humans and likely to be relevant in HLBS disorders…”
to set the stage for an extended investigation of this phenomenon.

## Key facts

- **NIH application ID:** 10074591
- **Project number:** 5R21HL150575-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Peter A Nigrovic
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $185,995
- **Award type:** 5
- **Project period:** 2020-01-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074591

## Citation

> US National Institutes of Health, RePORTER application 10074591, Impact of emperipolesis on platelet function (5R21HL150575-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074591. Licensed CC0.

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