# Role of purinergic signaling in pediatric multi-organ failure

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $394,503

## Abstract

Infection leading to very severe or multiple organ dysfunction is called severe sepsis, a leading cause of death
in children. Worsening organ dysfunction develops due to an impaired host response that can progress even
after clearance of the pathogen. Most therapeutic approaches to improve outcome in septic patients have
resulted in disappointment. Progress in this field requires a better understanding of the reasons why the
immune response in critically ill children is impaired. Our previous work has revealed that endogenous ATP
release and autocrine purinergic signaling mechanisms regulate neutrophil (PMN) functions and that
exogenous ATP and adenosine disrupt normal PMN functions. Based on this work, we hypothesize that
infections and tissue damage elevate plasma ATP levels, which impairs the ability of PMNs to eliminate
bacteria and promotes PMN-mediated tissue damage that causes MODS in pediatric critical care patients.
Aim 1: Contribution of systemic ATP to MODS in pediatric patients: First, we will assess ATP and
adenosine levels in the plasma of pediatric patients with sepsis with varying degrees of MODS. Next, we will
study how these levels influence PMN functions that protect patients and functions that worsening MODS.
Aim 2: Does the purinergic system of pediatric PMNs contribute to MODS? Next, we will study how the
PMNs of children differ from adults with regard to the purinergic signaling mechanisms that regulate protective
and harmful PMN functions.
Aim 3: Possible therapeutic targets for sepsis-related MODS: Finally, we will study how purinergic
signaling can be targeted to improve the protective functions of PMNs and to minimize collateral damage to
host organs.
We expect to find that innate differences in plasma ATP levels and purinergic signaling impair PMNs of
children, making them susceptible to infections. Common pathogens in children produce cytolysins that further
increase systemic ATP levels and PMN dysregulation, preventing antimicrobial host defenses and promoting
collateral tissue damage and MODS. Blocking ATP release or removal of systemic ATP are promising
therapeutic strategies to restore PMN function and reduce the risks of severe MODS during infection.

## Key facts

- **NIH application ID:** 9897607
- **Project number:** 5R01HD098363-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** WOLFGANG G JUNGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $394,503
- **Award type:** 5
- **Project period:** 2019-03-20 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897607

## Citation

> US National Institutes of Health, RePORTER application 9897607, Role of purinergic signaling in pediatric multi-organ failure (5R01HD098363-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897607. Licensed CC0.

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