# Neutrophil Survival and Demise During Inflammatory States

> **NIH NIH P01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $642,894

## Abstract

Abstract
Interleukin-1b is a pro-inflammatory cytokine in cardiovascular disease (CVD) contributing to life-threatening
cardiovascular events including myocardial infarction and stroke. Interleukin-1a also contributes to disease. The
cell types and signaling pathways that control IL-1a/b production remains to be comprehensively evaluated. This
study will investigate the neutrophil lineage in cardiovascular disease and their role in IL-1a/b production.
Neutrophil accumulation in tissues is a hallmark feature of many acute and chronic inflammatory diseases,
including coronary artery disease. Despite our broad understanding of the factors controlling neutrophil
production and function, we lack a comprehensive understanding of cell death signaling in the neutrophil lineage
at steady state and during inflammation. In patients with coronary artery disease, neutrophils accumulate in
atherosclerotic plaques, and are enriched in areas that are prone to rupture and intraplaque hemorrhage. In
mouse models of coronary artery disease (CAD), atherosclerotic plaques feature an accumulation of neutrophils
in early and advanced stages of disease, and neutrophil depletion impairs the early recruitment of monocytes to
the aortic arch and the progression of atherosclerosis. We hypothesize that neutrophils release IL-1 in CAD by
engaging the NLRP3 inflammasome, the Caspase-8-regulated apoptosis pathway, or the MLKL-regulated
necroptotic pathway. The control of Caspase-8-dependent apoptosis and IL-1 release by Bcl-2 family members
will be evaluated in neutrophil lineage cells including neutrophil progenitors (NePs), immature neutrophils, and
mature neutrophils. The effects of CAD on IL-1 production and cell death signaling in human neutrophil lineage
cells will be assessed. This research will identify pro-survival signals in coronary artery disease increasing
neutrophil longevity, and pro-death signals that control IL-1 production, formation of neutrophil extracellular traps,
release of mitochondria, and inflammatory forms of cell death.

## Key facts

- **NIH application ID:** 10270899
- **Project number:** 1P01HL152958-01A1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** HAROLD M HOFFMAN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $642,894
- **Award type:** 1
- **Project period:** 2021-08-16 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10270899

## Citation

> US National Institutes of Health, RePORTER application 10270899, Neutrophil Survival and Demise During Inflammatory States (1P01HL152958-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10270899. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*