# Role of RAGE and Necroptosis in Transfusion Mediated Lung Inflammation

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $407,500

## Abstract

   
DESCRIPTION (provided by applicant): Recent epidemiologic studies have demonstrated increased morbidity, mortality, and the development of Acute Respiratory Distress Syndrome (ARDS) associated with red blood cell (RBC) transfusions in the critically ill, yet the mechanisms underlying this association remain unknown. Our data demonstrate that banked RBCs induce necroptosis (a form of regulated necrotic cell death) of lung endothelial cells and enhance susceptibility to subsequent injury. We have previously demonstrated that the proinflammatory receptor for advanced glycation endproducts (RAGE) mediates lung endothelial dysfunction following RBC transfusion. The overall goal of this proposal is to elucidate the role of RAGE in RBC-induced necroptosis. In Specific Aim 1 the role of RAGE in sensing necroptotic stimuli will be examined in vitro and in a micro-engineered model of human lung. Specific Aim 2 will explore the role of intracellular RAGE in necroptosis execution. Lastly, Specific Aim 3 will examine the in vivo effects of RBC- induced necroptosis on lung injury using animal models. Knowledge derived from these studies will elucidate some of the mechanisms by which RBCs enhance susceptibility to lung injury and hopefully lead to novel therapies to prevent the morbidity associated with RBC transfusions.

## Key facts

- **NIH application ID:** 9838286
- **Project number:** 5R01HL126788-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Nilam S. Mangalmurti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $407,500
- **Award type:** 5
- **Project period:** 2015-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838286

## Citation

> US National Institutes of Health, RePORTER application 9838286, Role of RAGE and Necroptosis in Transfusion Mediated Lung Inflammation (5R01HL126788-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9838286. Licensed CC0.

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