# Differentiation and Function of Monocytes and Macrophages

> **NIH NIH R37** · WASHINGTON UNIVERSITY · 2022 · $393,750

## Abstract

Resident MΦs naturally reside freely floating in peritoneal fluid. To counteract the problem that
phagocytosis of cargo is inefficient in fluid, peritoneal MΦs produce Factor V to raise its local
levels and facilitate formation of interstitial clots upon induction of inflammation. The clots in turn
bring MΦs and microbes out of the fluid phase and into a 3-D environment together. This clotting
reaction operates with induced MΦ adhesion onto mesothelial membranes to collectively account
for the classical "MΦ disappearance reaction" (MDR). MDR in the peritoneum may also require
inflammasome activation, which may then lead to cell death that accounts for an extended period
of MΦ disappearance. Indeed, when the stimulus inciting the MDR is robust, Factor V+ resident
MΦs disappear for several weeks, likely leaving the peritoneal cavity susceptible to future
infectious and noninfectious threats for rather long durations. We will study possible links between
death and coagulation and use lineage tracing models to determine how resident MΦs repopulate.
Furthermore, we will investigate the idea that the peritoneal cavity is left susceptible to
immunological challenges during the long duration of MΦ loss following MDR. A prolonged period
of MΦ loss following a robust MDR may leave the body cavity vulnerable to infection. It may also
promote progression of other diseases associated with altered immunity, like cancers. In
particular, ovarian cancer is associated with the peritoneal cavity, where it often metastasizes and
expands. Human ovarian cancers are considered one of the most procoagulant tumors. If human
counterparts to the Factor V+ MΦs exist, which we will study herein, such cells might limit tumor
expansion clinically, as observed in mice. Overall, we will test the hypothesis that Factor V+
resident peritoneal macrophages protect the peritoneal cavity from microbial pathogens but also
against ovarian tumors and that the procoagulant activity of these macrophages, if linked to MDR
by a microbial or inflammatory trigger, may set up a state of enhanced susceptibility to tumor
growth due to loss of tumor-restricting MΦs.
RELEVANCE (See instructions):
Serious clinical conditions can arise in the peritoneal cavity, ranging from the initiation and progression of
sepsis to cancer. These diverse conditions rely on a functional immune compartment in the peritoneal
space, but there is much that remains to be defined to better combat diseases in this space. This
application focuses on host defense mediated by resident peritoneal macrophages.

## Key facts

- **NIH application ID:** 10308379
- **Project number:** 5R37AI049653-22
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Gwendalyn J Randolph
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $393,750
- **Award type:** 5
- **Project period:** 2011-09-15 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10308379

## Citation

> US National Institutes of Health, RePORTER application 10308379, Differentiation and Function of Monocytes and Macrophages (5R37AI049653-22). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10308379. Licensed CC0.

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