# Braking Macrophage Cell-Cell Fusion in the Foreign Body Response

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2022 · $205,000

## Abstract

By virtue of their versatility and plasticity, macrophages have the ability to undergo phenotypic
and functional changes in response to microenvironmental cues. One such change is the
formation of multinucleated giant cells via intercellular fusion triggered by certain bacterial or
parasitic infections or implantation of medical devices to induce a foreign body response. We
and others have shown that the transmembrane protein CD13 is a multifunctional molecule
that regulates diverse processes such as tumor cell invasion, immune cell trafficking, receptor
mediated endocytosis and recycling and organization of the actin cytoskeleton. In our
preliminary data, we demonstrate that despite a relatively normal distribution of hematopoietic
components in bone marrow and periphery, CD13KO mice have reduced bone mass with
increased osteoclast (OC) numbers per bone surface area but normal bone formation
parameters. In vitro induction of CD13-deficient myeloid progenitors generated from bone
marrow resulted in hyperfusion to generate multinucleated giant cells (MGCs) or OCs that
were considerably larger in size, contained many more nuclei than those from wild type
progenitors, suggesting that CD13 is a component of common fusion pathways shared by
MGC and OC. We observed that while expression of the key fusion proteins, dynamin and
DC-STAMP, are typically downregulated in mature cells post-fusion, expression of these
proteins is sustained at high levels in multinucleated cells lacking CD13. Thus, CD13 acts as
a brake to restrain a common cell-cell fusion pathway and may be a novel therapeutic target
in pathological conditions mediated by abnormal cell fusion. In this proposal, we will identify
the CD13-dependent mechanisms, molecules and signaling pathways involved in cell-
cell fusion in macrophages undergoing giant cell fusion (Aim 1) and the potential for
fusion-blocking anti-CD13 monoclonal antibodies as therapeutics in vitro and in vivo (Aim
2). We will use our extensive panels of wild type and CD13 knock out primary cells of
mouse and human origin, CD13 blocking or activating antibodies, novel CRISPR-deleted
CD13KO myeloid cell lines along with confocal and spinning disk microscopy and
CD13 knockout mouse models to address these questions.

## Key facts

- **NIH application ID:** 10373536
- **Project number:** 1R21AI159592-01A1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Mallika Ghosh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $205,000
- **Award type:** 1
- **Project period:** 2021-11-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373536

## Citation

> US National Institutes of Health, RePORTER application 10373536, Braking Macrophage Cell-Cell Fusion in the Foreign Body Response (1R21AI159592-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10373536. Licensed CC0.

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