# Infarct macrophage secretome components coordinate neutrophil degranulation and attenuate wall thinning

> **NIH NIH F31** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $20,556

## Abstract

Abstract
The cardiac wound healing response to myocardial infarction (MI) encapsulates inflammatory, proliferative, and
maturation phases. Neutrophil degranulation is a major component of the inflammatory phase, inducing both
tissue degradation and inflammation amplification. Neutrophil granules released into the infarct region contain
a series of enzymes including, but not limited to, matrix metalloproteinases (MMPs), cathepsins, and serine
elastase. The main function of these proteases is to breakdown extracellular matrix (ECM) to permit removal of
necrotic myocyte debris from the infarct to make way for new ECM scar formation. Excessive protease activity
can yield excessive infarct wall thinning. Macrophages and neutrophils communicate throughout the wound
healing process, although details on how and why have not been fully elucidated. The goal of this project is to
understand how macrophage communication to the neutrophil contributes to MI wound healing. My preliminary
studies suggest that murinoglobulin-1 in the macrophage secretome attenuates while galectin-3 exacerbates
neutrophil degranulation. The overall net effect to coordinate neutrophil cell physiology is determined,
therefore, by the composition of the macrophage secretome. Aim 1 will test the hypothesis that macrophage
produced murinoglobulin-1 (MUG-1), an α2-macroglobulin homolog in mice, attenuates neutrophil
degranulation to limit infarct wall thinning. Aim 2 will test the hypothesis that macrophage produced galectin-3
promotes neutrophil degranulation to fuel infarct wall thinning. Aim 3 will test the hypothesis that the
combination of MUG-1 stimulation with galectin-3 inhibition will synergistically reduce wall thinning and improve
cardiac remodeling. Innovation lies in the evaluation of macrophage communication to the neutrophil after MI.
We will integrate multi-discipline approaches to explore the mechanisms whereby neutrophils regulate
remodeling through effects from the macrophage. This study will drive forward the understanding of the cellular
basis of LV remodeling and identify novel intervention targets directed at neutrophils or macrophages.

## Key facts

- **NIH application ID:** 10139777
- **Project number:** 1F31HL156315-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Michael J Daseke
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $20,556
- **Award type:** 1
- **Project period:** 2021-03-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10139777

## Citation

> US National Institutes of Health, RePORTER application 10139777, Infarct macrophage secretome components coordinate neutrophil degranulation and attenuate wall thinning (1F31HL156315-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10139777. Licensed CC0.

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