# Pannexin-1 Signaling in Lung Ischemia-Reperfusion Injury

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $558,452

## Abstract

Project Summary
The success of lung transplantation is limited by high rates of primary graft dysfunction due to
ischemia-reperfusion injury (IRI) characterized by robust inflammation, alveolar damage, and
vascular permeability. IRI is also a risk factor for late graft rejection (bronchiolitis obliterans), the
major cause of mortality beyond one year of transplant. ATP is a nucleotide released in large
amounts after acute lung injury such as IRI and serves as a “danger signal” to mediate
inflammation. Recent studies reveal that cells can actively release ATP in a controlled manner
through pannexin 1 (Panx1) channels to signal through purinergic P2X or P2Y receptors. Our
data suggest that Panx1 on endothelial cells (ECs) is an important mediator of lung injury and
vascular inflammation after IR and may be a major source of extracellular ATP after IR. Thus
this proposal will test the overall hypothesis that EC Panx1 signaling is a major, early
inflammatory mediator of lung IRI via release of ATP resulting in endothelial barrier dysfunction,
vascular inflammation and leukocyte infiltration. Specific Aim 1 will determine if EC Panx1
signaling mediates lung IRI via ATP release and whether the P2X7 receptor is a major
determinant of IRI. Specific Aim 2 will determine if Panx1 signaling mediates leukocyte
activation and infiltration during lung IRI. The role of Panx1 and specific purinergic receptors on
alveolar macrophages will be deciphered as well as whether Panx1 mediates neutrophil
transendothelial migration. Specific Aim 3 will determine if pharmacologic inhibition of Panx1 will
prevent IRI after lung transplantation using a murine orthotopic lung transplant model. This
transplant model will also be utilized to decipher the role of Panx1 signaling in donor versus
recipient cells as well as in ECs and alveolar macrophages after transplantation. There currently
are no preventative therapies for IRI, and our studies will provide novel insight into mechanisms
or lung IRI and will define Panx1 as a novel therapeutic target for the prevention of IRI after lung
transplantation.

## Key facts

- **NIH application ID:** 9898429
- **Project number:** 5R01HL133293-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Victor E Laubach
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $558,452
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898429

## Citation

> US National Institutes of Health, RePORTER application 9898429, Pannexin-1 Signaling in Lung Ischemia-Reperfusion Injury (5R01HL133293-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9898429. Licensed CC0.

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