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"The Ring”

Weiguo Cui and Agnès Vignery

Bone marrow-derived macrophages were cultured in the presence of M-CSF and RANKL for 8 days, then fixed and reacted with phalloidin-Alexa 568 and Dapi. Active multinucleate osteoclasts adhere to bone via an actin-rich sealing zone, which is called a “ring” because it delineates their outer ridge. The pictures were captured with a Leica TCS SP5 AOBS spectral confocal microscope (Mannheim, Germany).

The fusion of macrophages is a rare event, which leads to the formation of multinucleate osteoclasts that are essential for the development, remodeling and repair of bone. Dysfunctional osteoclast activity is often the cause of bone diseases such as osteoporosis. The fusion of macrophages also leads to the formation of multinucleate giant cells that form in response to a foreign body, such as a pathogen or an implant. Research in our laboratory focuses on the molecular mechanisms of macrophage fusion.

We have used in vivo and in vitro macrophage fusion assays and generated monoclonal antibody to identify the potential members of the fusion machinery. We have cloned MFR/SIRPα, the expression of which is transiently but highly induced in macrophages at the onset of fusion in vitro and in vivo. We have also reported CD47 as the ligand for MFR, and CD44 as a molecule also highly and transiently expressed at the onset of fusion. We have used genome-wide cDNA microarrays to identify the genes that belong to the fusion machinery and found that CD200 is highly expressed in osteoclast and giant cells, but only at the onset of fusion of macrophages, which do not express CD200. Our goal is to define the role of the molecules we identified in the fusion of macrophages. The understanding we gained about macrophage-macrophage fusion is being applied to studies on macrophage fusion with tumor cells and somatic cells, such as hepatocytes.