Disruption of filamentous actin inhibits human macrophage fusion

• Published in: The FASEB journal Vol. 13; no. 8; p. 823
• Main Authors: DeFife, K M, Jenney, C R, Colton, E, Anderson, J M
• Format: Journal Article
• Language: English
• Published: United States 01.05.1999
• Subjects: Actins - metabolism; Cell Fusion - drug effects; Cell Fusion - physiology; Cell Movement - drug effects; Cell Size - drug effects; Cytochalasin B - pharmacology; Cytochalasin D - pharmacology; Foreign-Body Reaction - etiology; Foreign-Body Reaction - metabolism; Foreign-Body Reaction - pathology; Giant Cells, Foreign-Body - drug effects; Giant Cells, Foreign-Body - metabolism; Giant Cells, Foreign-Body - pathology; Humans; In Vitro Techniques; Interleukin-13 - pharmacology; Lectins, C-Type; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Mannose-Binding Lectins; Microscopy, Confocal; Phagocytosis - physiology; Receptors, Cell Surface - physiology
• ISSN: 0892-6638
• DOI: 10.1096/fasebj.13.8.823

The foreign body reaction to implanted biomaterials, characterized by the presence of macrophages and foreign body giant cells (FBGC), can result in structural and functional failure of the implant. Recently, we have shown that interleukin-4 and interleukin-13 can independently induce human macrophage fusion to form FBGC via a macrophage mannose receptor (MR) -mediated pathway. The MR is believed to mediate both endocytosis of glycoproteins and phagocytosis of microorganisms, which bear terminal mannose, fucose, N-acetylglucosamine, or glucose residues. Polarization of microfilaments to closely apposed macrophage membranes as observed with fluorescence confocal microscopy led us to ask whether MR-mediated fusion occurred via a filamentous actin-dependent pathway. Cytochalasins B and D and latrunculin-A, agents that disrupt microfilaments, inhibited macrophage fusion in a concentration-dependent manner. The concentrations of cytochalasins D and B that inhibited fusion did not significantly decrease macrophage adhesion, spreading, or motility but did inhibit internalization of Candida albicans during interleukin-13-enhanced, MR-mediated phagocytosis. Very low concentrations of cytochalasin B (< 2 microM) induced a slight enhancement of macrophage fusion. Taken together, the results of this study suggest that cytokine-induced, MR-mediated macrophage fusion requires an intact F-actin cytoskeleton and that the mechanism of fusion is similar to phagocytosis.--DeFife, K. M., Jenney, C. R., Colton, E., Anderson, J. M. Disruption of filamentous actin inhibits human macrophage fusion.