IDENTIFICATION OF AN INDUCIBLE SURFACE-MOLECULE SPECIFIC TO FUSING MACROPHAGES

Multinucleated giant cells and osteoclasts arise through the fusion of mononuclear phagocyte precursors, To elucidate the mechanism by which cells of monocytic lineage fuse and differentiate into giant cells an d osteoclasts, we hypothesized that, as with other cell fusion events, specific surface molecules mediate the adhesion/fusion process, it ha s been observed that macrophages can be induced to fuse with one anoth er in response to specific stimuli or when placed in a specific microe nvironment. The formation of giant cells is primarily associated with chronic inflammatory reactions and tumors, while osteoclasts different iate on bone which they resorb, The fact that, under normal conditions , macrophages and monocytes fail to fuse in regions and tissues where they are present in large numbers suggests the regulated and transient expression of potential fusion molecules, To identify such a fusion-a ssociated molecule, we established a macrophage fusion assay and gener ated monoclonal antibodies (mAbs) that alter the fusion of macrophages in vitro. We selected four mAbs that each had the ability to block th e fusion but not the aggregation of macrophages ill vitro. All four an tibodies recognize surface proteins of 150 kDa, The expression of the antigens recognized by all four mAbs is restricted to macrophages that have been induced to fuse in vitro and in vivo and is inducible, tran sient, and regulated, as neither nonfusing macrophages nor macrophages fused in vitro express these antigens, These results support the hypo thesis that macrophage fusion is mediated by specific fusion/adhesion molecules and also provide a means to study the molecular mechanisms o f macrophage fusion.