# Chlorinated lipids in sepsis

> **NIH NIH R01** · SAINT LOUIS UNIVERSITY · 2021 · $59,387

## Abstract

Sepsis is a major cause of morbidity and mortality in both adults and children with >1.6 million cases per year
in the United States. Neutrophils are key early responders to infection. Neutrophils eliminate microbes by
phagocytosis and by oxidant-mediated killing. Neutrophil myeloperoxidase (MPO) produces the potent oxidant,
hypochlorous acid (HOCl), which reacts with both microbial and host molecular targets including lipids. PI Dr.
David Ford has shown HOCl targets the vinyl ether bond of plasmalogen lipids, resulting in the production of 2-
chlorofatty aldehyde (2-ClFALD) and other chlorolipids, including 2-chlorofatty acid (2-ClFA), in response to
leukocyte activation. This led our multi-PI team during the previous grant interval to determine chlorolipids elicit
endothelial activation leading to leukocyte and platelet adherence, and to demonstrate chlorolipids associate
with ARDS and 30-day mortality in human sepsis. Our multi-PI group has accrued new preliminary data
showing that: 1) 2-ClFA modifies specific endothelial cell proteins, which may represent a new paradigm to
target for intervention of 2-ClFA-caused endothelial activation; 2) plasma levels of w-oxidation products of 2-
ClFA, 2-chlorodicarboxylic acids (2-ClDCAs), measured on admission to the intensive care unit (ICU) with
sepsis are elevated in patients that develop acute kidney injury (AKI); and 3) 2-ClDCA causes endothelial
dysfunction. The role of chlorolipids in sepsis is expanding, and these preliminary data indicate there are
knowledge gaps that need to be addressed in the proposed studies, which will test our overall hypothesis
that chlorolipids produced by activated neutrophils during sepsis are mediators of severe endothelial
dysfunction resulting in multiple organ failure. There are two specific aims. Specific Aim 1 will test the
hypothesis that chlorolipid-mediated dysfunction in human endothelial cells can be pharmacologically targeted.
Specific Aim 2 will test the hypothesis that plasma 2-ClDCA levels associate with specific organ dysfunctions
and death in human sepsis. Overall, a multi-disciplinary approach with our multi-PI team and Co-Is will
examine chlorolipids produced by activated neutrophils during sepsis as critical mediators of microcirculatory
dysfunction leading to organ failure, and test inhibitors of, and pathways activated by, chlorolipid-elicited
endothelial dysfunction as intervention points. This collaborative investigation has the potential to provide new
therapeutic and diagnostic targets for patients with sepsis.

## Key facts

- **NIH application ID:** 10378863
- **Project number:** 3R01GM115553-07S1
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** DAVID A. FORD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $59,387
- **Award type:** 3
- **Project period:** 2015-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378863

## Citation

> US National Institutes of Health, RePORTER application 10378863, Chlorinated lipids in sepsis (3R01GM115553-07S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10378863. Licensed CC0.

---

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