# Defining the temporospatial functions of neutrophils in acute airspace disease

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2024 · $21,501

## Abstract

Project Summary/Abstract
Inflammation and immune responses are critical in the body’s response to inflammatory injuries such as
infection or tissue damage. Leukocytes, cells of the immune system, are recruited to these sites of damage or
insult via a process known as the inflammatory cascade. In the inflammatory cascade, the step where
leukocytes migrate out of the blood and across the endothelium is known as transendothelial migration (TEM)
and occurs via interactions between leukocyte and endothelial PECAM and CD99. While much is known about
the inflammatory cascade and subsequent neutrophil function in the systemic circulation and tissue beds, the
process remains more elusive in the lungs. Understanding how types of leukocytes like neutrophils traffic from
their sites of synthesis through the vasculature, migrate through the endothelium into the lungs and perform
various functions (both pro-inflammatory and resolving) is of extreme importance due to the role of leukocytes
in inflammatory pathology. When in the tissue, neutrophils perform many functions as granulocytic cells,
resolving infection and insult, and are critical in ameliorating disease. However, they can also be damaging
mediators of disease in their own right, contributing to inflammatory damage and disruption of normal
physiological function. Two major forms of acute inflammatory airspace diseases in the lungs, gastric
aspiration pneumonia and bacterial bronchopneumonia, have high prevalence and mortality and currently have
no preventative therapies. The symptoms of these diseases in part are due to the crowding of the alveolar
space, impaired gas exchange, and damage by neutrophils, and as such, high neutrophil presence correlates
with adverse outcomes. However, neutrophils can also produce molecules known as specially pro-resolving
mediators (SPMs) that are anti-inflammatory. Previous work shows that recruitment and migration of
leukocytes in the lungs differs from the systemic circulation and neutrophil function is highly important in
disease progression. I aim to interrogate the mechanisms by which neutrophils undergo TEM in the lungs
during acute airspace disease and the functions they perform both individually and in concert with
macrophages in the tissue and vasculature. I hypothesize that transmigration can be used to better pathology
in infectious bronchopneumonia (Aim 1) and that there are populations of neutrophils that produce SPMs and
interact with macrophages during lung injury (Aim 2). This will provide key mechanistic insights on TEM and
function of neutrophils in the lungs, while also providing potential for therapeutic intervention and
characterization of neutrophil roles in acute inflammatory airspace diseases.

## Key facts

- **NIH application ID:** 10993516
- **Project number:** 1F31HL172345-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Maureen Haynes
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $21,501
- **Award type:** 1
- **Project period:** 2024-12-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993516

## Citation

> US National Institutes of Health, RePORTER application 10993516, Defining the temporospatial functions of neutrophils in acute airspace disease (1F31HL172345-01A1). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/10993516. Licensed CC0.

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