# The Role of Ischemia Reperfusion Injury in Lung Allograft Rejection

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $530,808

## Abstract

PROJECT SUMMARY
Survival rates after lung transplantation continue to lag substantially behind those observed after
transplantation of other solid organs. A major barrier to success of lung transplantation is primary
graft dysfunction, a form of acute lung injury that is mediated by ischemia reperfusion injury.
Primary graft dysfunction not only results in an increase in early morbidity and mortality, but it also
predisposes to chronic lung allograft dysfunction. We have developed new clinically relevant
mouse models of lung transplantation and novel intravital imaging approaches to examine
mechanistic links between primary graft dysfunction and rejection. In our previous funding period
we have discovered that monocytes play a central role in mediating primary graft dysfunction by
regulating neutrophil entry into the reperfused lung graft. Furthermore, we have described
mechanisms how neutrophilic uptake of endogenous ligands that are released from injured lungs
propagates primary graft dysfunction. In this application we propose to examine pathways that
result in the activation of monocytes and neutrophils in lung grafts and to uncover mechanisms
how these cells promote alloimmunity and graft rejection. In Aim 1 we will define mechanisms
that activate neutrophils upon graft infiltration. In Aim 2 we will analyze pathways that mediate the
activation and differentiation of monocytes in lung grafts. In Aim 3 we will examine interactions
between monocytes and T cells that can trigger graft rejection.

## Key facts

- **NIH application ID:** 9969086
- **Project number:** 5R01HL094601-11
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Andrew Eric Gelman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $530,808
- **Award type:** 5
- **Project period:** 2009-09-02 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969086

## Citation

> US National Institutes of Health, RePORTER application 9969086, The Role of Ischemia Reperfusion Injury in Lung Allograft Rejection (5R01HL094601-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9969086. Licensed CC0.

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