# The role of Poldip2 in macrophages during sepsis-induced lung injury

> **NIH NIH F32** · EMORY UNIVERSITY · 2020 · $75,858

## Abstract

Sepsis constitutes a major cause of morbidity and mortality worldwide by causing life-threatening 
organ dysfunction, with almost 50% of patients developing acute lung injury and respiratory failure 
being a major cause of death. Current evidence suggests multiple processes involved in 
sepsis-induced acute lung injury, including endothelial barrier disruption with subsequent 
infiltration by immune cells. Recent studies also suggest a special role for alveolar macrophages 
in the progression of lung inflammation through their influence on other immune cells in the lung. 
However, the exact molecular mechanisms of sepsis-induced acute lung injury remain unknown and only 
a handful of potential interventions have been investigated. Polymerase-δ-interacting protein 2 
(Poldip2) is a multifunctional protein originally described over a decade ago as a 368 amino acid 
binding partner of DNA polymerase delta and proliferating cell nuclear antigen. Work by our lab 
showed that Poldip2 depletion in mice inhibited lipopolysaccharide (LPS)-induced infiltration
of leukocytes into the alveolar space and strongly reduced endothelial permeability, resulting
in improved mortality. Here we hypothesize that lower Poldip2 levels also affect the function of 
the immune cells and macrophages in particular, thus decreasing sepsis-induced lung injury. We will 
test our hypothesis in two specific aims. In the first aim, we will investigate the role of Poldip2 
in immune cell recruitment during sepsis-induced lung injury. We will evaluate the total number of 
alveolar macrophages at baseline as well as the total count and percentage of pro-inflammatory and 
anti-inflammatory macrophages after LPS injection in Poldip2+/+ and Poldip2+/- mice. We will also 
assess the levels of chemokine secretion by Poldip2+/+ and Poldip2+/- macrophages and their effect 
on neutrophil migration. In the second aim, we will investigate the molecular mechanisms underlying 
the differences in macrophage activation in Poldip2 deficient mice during sepsis. We will explore 
classic pro-inflammatory and anti-inflammatory activation pathways in Poldip2+/+ and Poldip2+/- 
macrophages as well as alternative pathways previously implicated in sepsis-induced lung injury. 
Completion of these aims will result in a better understanding of the role of Poldip2 in 
sepsis-induced acute lung injury and will provide insight into new potential therapeutic targets.

## Key facts

- **NIH application ID:** 9911114
- **Project number:** 1F32HL151133-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Elena Dolmatova
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $75,858
- **Award type:** 1
- **Project period:** 2020-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9911114

## Citation

> US National Institutes of Health, RePORTER application 9911114, The role of Poldip2 in macrophages during sepsis-induced lung injury (1F32HL151133-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9911114. Licensed CC0.

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