# Blood Cell Lipoxygenase Products -- Formation and Action

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $430,310

## Abstract

7. Project Summary/Abstract
Blood-borne bacteria can lead to inflammation, coagulation, sepsis and mortality. New non-
immunosuppressive treatments are needed. Phagocytes are the major white blood cells [neutrophils (PMN),
monocytes and macrophages (MF)] key to successful defense as well as clearance of debris and bacteria.
Ideally acute inflammation is protective and normally self-limited to resolve on its own, namely timely
resolution. It is now appreciated that, when uncontrolled, inflammation is a component of many widely
occurring chronic diseases. This proposal’s overall goal is to elucidate the lipid mediators that link coagulation
to resolution of inflammation. With support from GM38765, we obtained the first evidence (and now other
investigators) that resolution is an active process with identification of novel resolution phase mediators and
their receptors. This new super-family of specialized pro-resolving mediators (SPM) includes resolvins (Rv),
protectins (PD) and maresins (MaR). Each of the main SPM have proven to be anti-inflammatory, pro-resolving
and stimulate killing of bacteria. It’s now evident that resolution of inflammation and its link(s) to blood
coagulation are uncharted and critically needed. This proposal is based on innovative findings giving new
concepts where we uncovered an entirely new link between coagulation-resolution of inflammation
involving specific SPM. We identified a specific cluster of SPM produced during coagulation using a new lipid
mediator-metabolipidomics profiling approach devised in this lab. We found hemorrhagic exudates increase
SPM in mice, and in human whole blood this specific SPM cluster (RvE1, RvD1, RvD5, LXB4 and MaR1) is
temporally produced. The cluster includes maresin 1 (MaR1), a potent regulator of PMN and MF responses in
resolution. Unique and innovative features of this proposal include systematic identification of resolution
pathway mediators together with resolution indices to assess in hemorrhagic exudates, cells and chemical
mediators. Our mission is to test the following new hypothesis: Coagulation of blood temporally activates a
specific cluster of SPM (RvE1, RvD1, RvD5, LXB4 and MaR1) linking coagulation to resolution and
innate host defense. Together with resolvins and their receptors, MaR1 is a potent agonist governing
local phagocyte resolution responses via new receptors required for effective microbial killing. To
address this, a research design of 3 specific aims and multi-pronged approach will be carried out: 1) Profiling
of hemorrhagic exudates and coagulation activating SPM-resolution; 2) Evidence for novel MaR1 pro-resolving
receptors; and 3) Validation of specific MaR1 receptor pro-resolving function(s). Since new anti-inflammatories
are needed that are not immunosuppressive, our results from these innovative studies will impact this scientific
area and patient care by providing rigorous evidence for novel resolution pathways and agonist-driven
mechanisms controlling...

## Key facts

- **NIH application ID:** 9975186
- **Project number:** 5R01GM038765-34
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Charles Nicholas Serhan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $430,310
- **Award type:** 5
- **Project period:** 1987-07-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975186

## Citation

> US National Institutes of Health, RePORTER application 9975186, Blood Cell Lipoxygenase Products -- Formation and Action (5R01GM038765-34). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9975186. Licensed CC0.

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