# Vascular endothelial cells and macrophages coordinate neutrophil trafficking in inflammation

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $387,297

## Abstract

Title: Vascular endothelial cells and macrophages coordinate neutrophil trafficking in inflammation
Abstract
Many pathological conditions occur due to or involve deregulated immune cell trafficking and/or effector function.
In particular, tissue accumulation of innate immune cells termed neutrophils (PMN) while essential for host
defense and tissue homeostasis, often leads to exacerbated inflammation.
Crossing of the endothelial barrier is the first critical regulatory step in tissue PMN effector function. Many
receptor-ligand interactions involved this cascade have been well-defined, however, cues that initiate and
terminate this process are less understood. Our data identified a novel synergistic function of endothelial cells
(ECs) and interstitial macrophages (Mϕs) in regulating this importnant process in inflamed mucosa. We found
that EC-specific cues attract Mϕs to the vessel wall, and that Mϕs extend cellular protrusions to form transient
junctions with ECs. Through these binding interactions and the release of extracellular vesicles (EVs), which
transport regulatory microRNAs, Mϕs can transduce the necessary signaling events in ECs to preferentially
accommodate PMN TEM. Thus, the overall goal of this proposal is to define mechanisms and signaling events
that regulate interstitial Mϕ recruitment and contact with the vessel wall to locally prime EC responses and guide
PMN TEM in inflamed mucosa. We will utilize state-of-the-art 2-photon intravital microscopy (2pIVM), relevant
reporter and KO mice in models of mucosal inflammation to 1. Determine how interstitial Mϕs are recruited to
interact with vascular ECs in inflamed tissue. 2. Define mechanisms by which Mϕs prime vascular ECs to form
PMN TEM hot spots. 3. Determine the extent to which Mϕ-priming of vascular ECs (hot spot formation) is required
for PMN TEM and resolution of tissue inflammation. Our studies will define new mechanisms of PMN trafficking,
and likely identify new molecular targets to improve resolution of inflammation.

## Key facts

- **NIH application ID:** 10298564
- **Project number:** 1R01AI153568-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ronen Sumagin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $387,297
- **Award type:** 1
- **Project period:** 2021-06-04 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10298564

## Citation

> US National Institutes of Health, RePORTER application 10298564, Vascular endothelial cells and macrophages coordinate neutrophil trafficking in inflammation (1R01AI153568-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10298564. Licensed CC0.

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