# Role of intravascular ERO1@ in acute lung injury

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $379,898

## Abstract

Project Summary
Acute lung injury (ALI) is a life-threatening condition, which affects > 200,000 patients annually in the U.S. It is
associated with pneumonia, sepsis, and trauma, leading to pulmonary insufficiency and eventually multisystem
organ failure. Since excessive recruitment of activated neutrophils to lung microvessels is a primary cause of
ALI, a better understanding of the mechanism mediating neutrophil-endothelial cell interactions will provide
insight into developing an effective therapeutic for treating ALI. We previously demonstrated that intravascular
protein disulfide isomerase (PDI) enhances the ligand-binding activity of neutrophil and platelet surface receptors
and leads to intravascular cell-cell interactions during vascular inflammation. To elucidate how extracellular PDI
activity is regulated and whether the regulatory mechanism contributes to the pathology of ALI, we have found
that endoplasmic reticulum oxidoreductin 1α (ERO1α, a key oxidase of PDI in the ER) promotes neutrophil
recruitment during vascular inflammation. In this proposal, we will test the hypothesis that intravascular ERO1α
enhances the ligand-binding function of neutrophil adhesion receptors by modifying disulfide bonds, inducing
neutrophil recruitment to sites of acute lung inflammation. In Aim 1, we will determine the mechanism by which
ERO1α regulates neutrophil-endothelial cell interactions. In Aim 2, we will utilize lung live imaging techniques to
investigate the pathological role of intravascular ERO1α in ALI. In Aim 3, using the blood of patients with acute
respiratory distress syndrome (ARDS), we will determine the contribution of ERO1α to the disease progression
and severity in patients with ARDS. These studies will employ biochemical, cell biological, genetic, and confocal
intravital imaging approaches. Since little is known about extracellular thiol-modifying machinery, the proposed
studies will identify an essential, yet unexplored, mechanism that promotes the pathogenesis of ALI/ARDS.

## Key facts

- **NIH application ID:** 10469645
- **Project number:** 5R01HL153047-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jaehyung Cho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $379,898
- **Award type:** 5
- **Project period:** 2020-09-21 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469645

## Citation

> US National Institutes of Health, RePORTER application 10469645, Role of intravascular ERO1@ in acute lung injury (5R01HL153047-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10469645. Licensed CC0.

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