Polarized distribution of Na+,K+-ATPase in giant cells elicited in vivo and in vitroA Vignery, T Niven-Fairchild, DH Ingbar and M Caplan Department of Orthopaedics, Yale University School of Medicine, New Haven, Connecticut 06511. Giant cell formation was analyzed to determine whether it results in the high level of Na+,K+-ATPase expression that characterizes multinucleated cells such as osteoclasts. Giant cells and fusing alveolar macrophages were subjected to morphological, immunological, and biochemical studies. Both subunits of the Na+,K+-ATPase were found to be present on the plasma membrane of giant cells. Their localization was restricted to the non-adherent domain of the cell surface. Dynamic studies of giant cell differentiation demonstrated that on culture and/or multinucleation, an increase in sodium pump alpha-subunit synthesis occurred and led to a high level of expression of Na pumps. Conversely, the adherent plasma membrane of giant cells was enriched in a lysosomal membrane antigen. This study demonstrates that culture and/or multinucleation induces a significant increase in the expression of sodium pumps. The polarized distribution of these pumps and of a lysosomal component suggests that fusing macrophages undergo biochemical and morphological alterations which prepare them for a new and specialized function in chronic inflammatory reactions. Giant cells may offer a suitable model system to study the differentiation of other related multinucleated cells, such as osteoclasts.
Volume 37,
Issue 8,
pp. 1265-1271,
08/01/1989
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W. Cui, J. Z. Ke, Q. Zhang, H.-Z. Ke, C. Chalouni, and A. Vignery The intracellular domain of CD44 promotes the fusion of macrophages Blood, January 15, 2006; 107(2): 796 - 805. [Abstract] [Full Text] [PDF] |
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A. K. McNally and J. M. Anderson Foreign Body-Type Multinucleated Giant Cell Formation Is Potently Induced by {alpha}-Tocopherol and Prevented by the Diacylglycerol Kinase Inhibitor R59022 Am. J. Pathol., September 1, 2003; 163(3): 1147 - 1156. [Abstract] [Full Text] [PDF] |
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A. K. McNally and J. M. Anderson {beta}1 and {beta}2 Integrins Mediate Adhesion during Macrophage Fusion and Multinucleated Foreign Body Giant Cell Formation Am. J. Pathol., February 1, 2002; 160(2): 621 - 630. [Abstract] [Full Text] [PDF] |
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K. M. DeFife, C. R. Jenney, E. Colton, and J. M. Anderson Cytoskeletal and Adhesive Structural Polarizations Accompany IL-13-induced Human Macrophage Fusion J. Histochem. Cytochem., January 1, 1999; 47(1): 65 - 74. [Abstract] [Full Text] |
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A. Gasser and J. Most Generation of Multinucleated Giant Cells In Vitro by Culture of Human Monocytes with Mycobacterium bovis BCG in Combination with Cytokine-Containing Supernatants Infect. Immun., January 1, 1999; 67(1): 395 - 402. [Abstract] [Full Text] [PDF] |
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C. Saginario, H. Sterling, C. Beckers, R. Kobayashi, M. Solimena, E. Ullu, and A. Vignery MFR, a Putative Receptor Mediating the Fusion of Macrophages Mol. Cell. Biol., November 1, 1998; 18(11): 6213 - 6223. [Abstract] [Full Text] |
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X. Han, H. Sterling, Y. Chen, C. Saginario, E. J. Brown, W. A. Frazier, F. P. Lindberg, and A. Vignery CD47, a Ligand for the Macrophage Fusion Receptor, Participates in Macrophage Multinucleation J. Biol. Chem., November 22, 2000; 275(48): 37984 - 37992. [Abstract] [Full Text] [PDF] |
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