# Platelet- mast cell interactions as determinants of the vascular pathology in septic shock.

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $463,512

## Abstract

Abstract:
Development of shock in sepsis defines a dramatic deterioration of clinical status and is linked to a significant
increase in morbidity and mortality rates. However, the cellular and molecular mechanisms determining the
vascular pathology of septic shock remain undefined.
Our past work established mast cells (MC) as key effector cells of vascular pathology in different
disease contexts. Because MC products are found in the plasma in shock but not during sepsis, this supports
that MC activation is a central event leading to septic shock. Employing state-of-the- art technologies such as
dynamic photoacoustic imaging of the microvasculature, we provide first evidence that MCs shape key features
of shock in sepsis: systemic hypotension, vascular leakage and microvascular perfusion abnormalities. In
addition, we elucidate that in sepsis MCs, which are located on the abluminal side of a relatively
impermeable endothelium, are stimulated by platelets, which can aggregate in their close proximity following
inflammatory triggers.
Based on these observations, we hypothesize that specific signaling interactions between platelets,
perivascular MCs and the endothelium drive the vascular pathology of septic shock. The objective of our work is
first to comprehensively define the mechanisms of MC-mediated vascular pathology in sepsis, second to
elucidate the specific mechanism by which platelets trigger MC responses and resultant vascular pathology
and lastly, to establish the clinical relevance of our findings in a cohort of septic patients.
Together, this project constitutes a key step towards our long-term goal to establish MC responses as
a biomarker of sepsis biology and to develop novel therapeutic strategies that may directly target the
mechanisms of disease progression in sepsis.

## Key facts

- **NIH application ID:** 10343476
- **Project number:** 1R01GM144606-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Soman N Abraham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $463,512
- **Award type:** 1
- **Project period:** 2021-09-22 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10343476

## Citation

> US National Institutes of Health, RePORTER application 10343476, Platelet- mast cell interactions as determinants of the vascular pathology in septic shock. (1R01GM144606-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10343476. Licensed CC0.

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