# Role of Macrophage Efferocytosis in Ozone-Induced ARDS

> **NIH NIH K08** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2022 · $222,505

## Abstract

Project Summary/Abstract
 Acute respiratory distress syndrome (ARDS) develops in some individuals as a sequela to indirect stress
on the lung from systemic infection (sepsis/endotoxemia). However, it is unclear why only some patients with
sepsis develop ARDS. One possible risk factor leading to ARDS in patients with sepsis is exposure to air
pollutants such as ozone. Recently, FDA acceptable environmental levels of ozone exposure have been
directly linked to the development of ARDS. Our overall goal is to elucidate the mechanisms underlying the
increased risk of developing ARDS following exposure to oxidants such as ozone. ARDS develops, in part,
due to an accumulation of dead and dying neutrophils and neutrophil-derived proinflammatory apoptotic bodies
in the lung. Under homeostatic conditions, these are removed by macrophages via a process known as
efferocytosis. We hypothesize that the increased risk of ARDS following ozone exposure is due impaired
efferocytosis. Moreover, this is exacerbated in individuals with genetic deficits in the pulmonary collectin,
surfactant protein D (SPD), which controls macrophage efferocytosis. To test this, we developed a novel
experimental model in which mice are exposed to inhaled ozone followed by intravenous (i.v.)
lipopolysaccharide (LPS), a bacterial-derived toxin released into the blood during sepsis (endotoxemia). Our
aims are to (1) Determine if ozone exposure and decreased SPD activity exacerbate inflammation and acute
lung injury (ALI) by impairing macrophage efferocytosis and (2) Determine if decreased SPD activity
exacerbates ozone-induced impairment of macrophage efferocytosis in humans. Wild type and lung-specific
conditional SPD knock out mice will be treated with ozone followed by LPS. Macrophage efferocytosis will be
measured by flow cytometry. The mechanistic pathways associated with oxidative stress, which is important in
ozone toxicity, will be identified using RNA sequencing (RNAseq). We will analyze lung inflammation and
macrophage efferocytosis in human subjects, stratified according to single nucleotide polymorphisms within the
SPD gene, following controlled ozone exposure. The results of these experiments will provide novel
mechanistic insights into the relationship between ozone exposure, macrophage function, SPD variation, and
susceptibility to ARDS. These studies are significant, as oxidants such as ozone have been implicated as a
risk factor the development of ARDS. The experiments, coursework, and structured mentorship proposed in
this application will provide the basis for an NIH R01 grant and initiate the PI's career in independent
translational research.

## Key facts

- **NIH application ID:** 10475712
- **Project number:** 7K08ES031678-03
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** JARED M. RADBEL
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $222,505
- **Award type:** 7
- **Project period:** 2020-09-22 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475712

## Citation

> US National Institutes of Health, RePORTER application 10475712, Role of Macrophage Efferocytosis in Ozone-Induced ARDS (7K08ES031678-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10475712. Licensed CC0.

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