# Plasmalogen-Derived Chlorinated Lipids: Mediators of Acute Lung Injury in Sepsis

> **NIH NIH F30** · SAINT LOUIS UNIVERSITY · 2020 · $50,520

## Abstract

ABSTRACT
This proposal will determine the relationships between lung injury and mortality in sepsis and plasmalogen-
derived chlorinated lipids, which are produced during the innate immune response. A significant cause of
morbidity and mortality in patients worldwide, sepsis is the systemic dysregulation of the immune response to
an initial infection and often leads to acute lung injury (ALI), other organ damage, and death. Host neutrophils
are a component of the innate immune system and are systemically activated during sepsis. Neutrophil
myeloperoxidase (MPO) is important in bacterial killing during sepsis. MPO catalyzes the production of
hypochlorous acid (HOCl) from hydrogen peroxide produced during the respiratory burst. HOCl, in turn, is a
powerful oxidant that targets microbes. However, HOCl may also react with host molecules, including the vinyl
ether bond of membrane plasmalogens. Plasmalogens are a class of glycerophospholipids with an aliphatic
chain connected to the glycerol backbone through a vinyl ether bond. When attacked by HOCl, the aliphatic
chain is liberated as chlorofatty aldehyde (2-ClFALD). 2-ClFALD can be oxidized to chlorofatty acid (2-ClFA)
under physiologic conditions. These compounds, designated as plasmalogen-derived chlorinated lipids, are
elevated in a variety of inflammatory conditions. A Ford lab manuscript in review demonstrates plasma 2-ClFA
predicts acute respiratory distress syndrome-associated mortality in sepsis. Other projects suggest
plasmalogen-derived chlorinated lipids elicit endothelial dysfunction, a major causative factor of ALI. We
hypothesize that plasmalogen-derived chlorinated lipids are critical mediators of acute lung injury and
mortality in sepsis through their role in eliciting endothelial dysfunction. Aim 1 of this proposal will use
a cecal slurry (CS) model of sepsis in rats to determine if plasmalogen-derived chlorinated lipid production
predicts sepsis outcomes, such as mortality, endothelial dysfunction, and lung injury. Mechanistic studies will
be employed to demonstrate causative roles of MPO and 2-ClFA in CS elicited mortality, endothelial
dysfunction, and lung injury. Aim 2 will determine that plasmalogen-derived chlorinated lipids cause
endothelial dysfunction and lung injury in the absence of sepsis by giving rats exogenous 2-ClFA. A click
chemistry analog of 2-ClFA will visualize the localization of the lipid to lung endothelium. Additional
experiments will examine 2-ClFA-elicited gut permeability. The mechanisms through which 2-ClFA elicits
endothelial dysfunction will also be explored using human lung endothelial cells. Current treatment regimens
for sepsis and sepsis-related ALI consist of antibiotics and supportive care, with a noticeable paucity in
treatments targeting the dysregulated host response. Further understanding of the mechanisms mediating
lung damage and pathology in sepsis is vital for the development of more efficacious treatments and
diagnostic strategies. A com...

## Key facts

- **NIH application ID:** 9967100
- **Project number:** 5F30HL142193-03
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** Daniel Pike
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9967100

## Citation

> US National Institutes of Health, RePORTER application 9967100, Plasmalogen-Derived Chlorinated Lipids: Mediators of Acute Lung Injury in Sepsis (5F30HL142193-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9967100. Licensed CC0.

---

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