# Contribution of mast cells to nitrogen mustard pulmonary toxicity

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $124,641

## Abstract

ABSTRACT
Mast cells are an innate immune cell found in high abundance at mucosal surfaces that interface with the
external environment where they play a major role as an immune sentinel to detect injury and insult. Sulfur
mustard (SM), a bi-functional alkylating agent, has been used as a chemical warfare agent and exposure
causes severe pulmonary, ocular and dermal toxicity. SM causes severe pulmonary damage upon inhalation
including damage to airways, tissue remodeling, massive immune cell recruitment, edema, etc. Much of the
toxicity to SM is attributed to its alkylating function and DNA damage, however, this does not explain the
massive inflammatory response observed nor is it known how these inflammatory responses are elicited in the
lung. We hypothesize that activation of mast cells by SM is an initiating step in recruitment and propagation of
immune responses in the lung. To test this hypothesis, we will expose wild-type or mast cell deficient mice to
nitrogen mustard (NM) (a surrogate for SM) to determine pulmonary responses including tissue damage,
inflammation and development of fibrosis. In addition, we will utilize mouse bone marrow-derived mast cells to
examine mechanisms by which NM leads to mast cell activation. Specifically, we will investigate whether NM
causes mast cell degranulation, lipid mediator production and/or cytokine production. Overall, our goal is to
establish a role for mast cells in regulating the pulmonary toxicity to NM thereby providing a novel therapeutic
target for prevention and/or treatment of the effects of these chemical warfare agents. The preliminary data
generated from this supplement will be used as the basis for a U01 application to the CounterAct program
focused on therapeutically targeting mast cells in SM toxicity.

## Key facts

- **NIH application ID:** 10092555
- **Project number:** 3R01ES019311-12S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Jared Michael Brown
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $124,641
- **Award type:** 3
- **Project period:** 2010-08-10 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10092555

## Citation

> US National Institutes of Health, RePORTER application 10092555, Contribution of mast cells to nitrogen mustard pulmonary toxicity (3R01ES019311-12S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10092555. Licensed CC0.

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