Year: 2023
Type: conference-abstract
Abstract: 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 (MGCs) via intercellular fusion triggered by certain bacterial or parasitic infections or implantation of medical devices that induces deleterious MGC formation in response to the foreign body. Despite advances in biomaterials, implants ultimately corrode to produce particles that initiate a foreign body response characterized by macrophage fusion into pro-inflammatory, Foreign Body Giant Cells that directly define the pathology of loosening of medical implants. We have shown that the transmembrane protein CD13 is a multifunctional molecule that regulates diverse processes such as cell-cell adhesion, receptor endocytosis and recycling and organization of the actin cytoskeleton, all of which are critical in cell-cell fusion. We demonstrate that subcutaneous foreign implants in CD13KO mice produce significantly more MGCs with increased levels of plasma pro-inflammatory cytokines. In vitro induction of fusion in CD13-deficient myeloid progenitors generated from bone marrow resulted in hyperfusion to generate MGCs that were considerably larger in size and contained many more nuclei than those from wild type progenitors, suggesting that CD13 regulates MGC formation at the stage of fusion. While expression of the key fusion proteins 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 prevent aberrant myeloid cell-cell fusion and may be a novel therapeutic target in pathological conditions mediated by abnormal cell fusion. Supported by grants from NIH (1R21 AI15)
Source: The Journal of Immunology
Authors: Mallika Ghosh, Fraser Mcgurk, Linda Shapiro
Institution: University of Connecticut
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4385685987