# Investigating Recruited Lung Macrophage Programming and Turnover in Self-Limited Versus Prolonged Lung Inflammation

> **NIH NIH F30** · UNIVERSITY OF COLORADO DENVER · 2023 · $36,939

## Abstract

PROJECT SUMMARY
The acute respiratory distress syndrome (ARDS) is characterized by severe lung inflammation and carries a
mortality of 30-40%. Some patients recover quickly while others improve slowly and often develop lung fibrosis.
The factors that drive these disparate outcomes are unclear. Pulmonary macrophages play key roles in the
pathogenesis of ARDS by releasing inflammatory cytokines, recruiting neutrophils, and releasing cytotoxic and
apoptotic factors which damage the lung epithelium. I hypothesize that inflammatory programming of pulmonary
macrophages and continuous recruitment of monocytes with inflammatory programming into the lung drive
prolonged inflammation and transient fibrosis in acute lung injury. Aim 1 of this proposal will use an existing
single-cell RNA sequencing (scRNAseq) dataset generated by the Janssen laboratory to test the hypothesis that
specific recruited monocyte-derived macrophage subsets from a mouse model of prolonged inflammation will
exhibit transcription profiles consistent with perpetuating inflammation and fibrosis. This transcription profile
would include expression of pro-inflammatory cytokines, chemokines, and cytotoxic factors. The transcriptional
programming of recruited macrophages in a prolonged inflammation model will be compared to recruited
macrophages from a model of self-limited inflammation. Aim 2 will use a compartment and lineage tracing mouse
model I have optimized to test the hypothesis that prolonged lung inflammation is characterized by continuous
recruitment of monocytes into the airspace and pulmonary interstitium that mature into pro-inflammatory
macrophages, with little proliferation in situ whereas self-limited inflammation is characterized by an early, single
wave of recruitment. Understanding the transcriptional profiles of recruited macrophage populations will provide
insight into the pathophysiology of limited versus prolonged lung inflammation. Defining the kinetics of monocyte
recruitment to the airspace and interstitium in limited versus prolonged inflammation will inform both the
pathophysiology of slowly resolving lung inflammation and the timeline for interventions.

## Key facts

- **NIH application ID:** 10749322
- **Project number:** 1F30HL167581-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Emily Mertens King
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $36,939
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10749322

## Citation

> US National Institutes of Health, RePORTER application 10749322, Investigating Recruited Lung Macrophage Programming and Turnover in Self-Limited Versus Prolonged Lung Inflammation (1F30HL167581-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10749322. Licensed CC0.

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