IL-4 promotes the formation of multinucleated giant cells from macrophage precursors by a STAT6-dependent, homotypic mechanism: contribution of E-cadherin

摘要: Multinucleated giant cells (MNG) are central players in the inflammatory response to foreign materials and adverse responses implants. IL-4 promotes formation of MNG from bone marrow-derived precursors vitro participates development body reaction vivo. Therefore, we investigated mechanism by which engulfment bodies. We found that generation was dependent on cell density expression STAT6; macrophages derived STAT6(-/-) mice were unable form IL-4. No soluble factors including CCL2 or supernatants IL-4-treated compensated for lack cultures. must remain present during full differentiation process STAT6(+/+) macrophage retained their ability differentiate into over time. These able internalize large particles efficiently, mononuclear do so. Furthermore, induced E-cadherin dendritic cell-specific transmembrane protein a STAT6-dependent manner. critical IL-4; an anti-E-cadherin antibody prevented MNG. In addition, progenitors failed fuse with STAT6(+/+), revealing need homotypic interaction. Thus, manner regulating surface E-cadherin, leading fusion incorporation