# Role of FABP5 in COPD Exacerbations

> **NIH NIH R01** · NATIONAL JEWISH HEALTH · 2022 · $495,444

## Abstract

PROJECT SUMMARY
 Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death in the United States
and its global prevalence continues to rise due to lack of an effective cure. Although cigarette smoke (CS) is by
far the most important risk factor of COPD, repeated and sustained infections are clearly linked to disease
pathogenesis (e.g., exacerbations). Interestingly, COPD exacerbations are a risk factor for having more
exacerbations, suggesting that a vicious cycle of ineffective resolution of inflammation predisposes individuals
for future episodes. Thus, identifying patients likely to have recurrent exacerbations may allow early
implementation of appropriate preventive strategies and would be an important new approach in the treatment
of the disease. We have discovered that Fatty Acid Binding Protein 5 (FABP5) is important for the resolution of
inflammation. However we do not fully comprehend the mechanisms behind FABP5 protective role in COPD
exacerbations. In this proposal we will focus on FABP5 in mononuclear phagocytes because these cells are at
the center of the processes required for the resolution of inflammation, including engulfment of apoptotic cells
and activation of anti-inflammatory nuclear receptors such as Peroxisome Proliferator-Activated Receptor γ
(PPARγ).
 Our preliminary studies indicate impaired apoptotic cell engulfment by alveolar macrophages and
reduced monocyte recruitment following bacterial infection in FABP5-/- mice. In addition, FABP5-/- mice have
increased bacterial and viral-induced lung inflammation, compared to wild type (WT) mice. The clinical
significance of these findings is supported by decreased FABP5 mRNA and protein levels in peripheral blood
mononuclear cells (PBMCs) of COPD patients, especially among those with a history of episodes of bronchitis,
pneumonia or COPD exacerbations and by the discovery of new SNPs in the FABP5 gene that are associated
with severe exacerbations. We hypothesize that decreased FABP5 following CS exposure worsens infection-
induced lung inflammation by preventing mononuclear lung phagocyte reprogramming, which is necessary for
resolution of lung inflammation in COPD exacerbations. To test this hypothesis, we propose 3 specific aims.
Under specific aim 1, we will test the hypothesis that CS impairs FABP5-mediated mononuclear lung phagocytes
recruitment and efferocytosis. Using WT, FABP5-/- or FABP5-/- mice complemented with FABP5 in mononuclear
phagocytes we will determine how FABP5 expression affects mononuclear phagocyte recruitment in response
to infection in the presence or absence of CS. We will also determine how FABP5 expression affects
mononuclear phagocyte engulfment capabilities following CS and/or infection in vivo and in vitro. Under aim 2,
we will test the hypothesis that FABP5/PPARγ interaction is necessary to promote resolution of inflammation
and return to homeostasis and determine whether CS impairs this interaction. We will manipulate FAB...

## Key facts

- **NIH application ID:** 10397397
- **Project number:** 5R01HL141264-04
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Fabienne Gally
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $495,444
- **Award type:** 5
- **Project period:** 2019-06-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397397

## Citation

> US National Institutes of Health, RePORTER application 10397397, Role of FABP5 in COPD Exacerbations (5R01HL141264-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10397397. Licensed CC0.

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