Multinucleated Giant Cells Are Specialized for Complement-Mediated Phagocytosis and Large Target Destruction
| Autor: | Siamon Gordon, Laura Helming, Fernando O. Martinez, Ronny Milde, Admar Verschoor, Mark B. Pepys, Andrzej Loesch, Julia Ritter, Glenys A. Tennent |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Macrophage colony-stimulating factor
Amyloid Phagocytosis Integrin alphaXbeta2 Bone Marrow Cells Mice Transgenic Complement receptor Giant Cells Article General Biochemistry Genetics and Molecular Biology Mice Cricetinae Macrophage fusion Animals Humans Macrophage lcsh:QH301-705.5 Mice Knockout Chemistry Macrophage Colony-Stimulating Factor Macrophages Receptors IgG Complement C3 M2 Macrophage ddc CD11c Antigen Rats Up-Regulation Cell biology Mice Inbred C57BL lcsh:Biology (General) Giant cell CD18 Antigens Immunology Tetradecanoylphorbol Acetate Interleukin-4 |
| Zdroj: | Cell Reports, Vol 13, Iss 9, Pp 1937-1948 (2015) Cell Reports |
| ISSN: | 2211-1247 |
| Popis: | Summary Multinucleated giant cells (MGCs) form by fusion of macrophages and are presumed to contribute to the removal of debris from tissues. In a systematic in vitro analysis, we show that IL-4-induced MGCs phagocytosed large and complement-opsonized materials more effectively than their unfused M2 macrophage precursors. MGC expression of complement receptor 4 (CR4) was increased, but it functioned primarily as an adhesion integrin. In contrast, although expression of CR3 was not increased, it became functionally activated during fusion and was located on the extensive membrane ruffles created by excess plasma membrane arising from macrophage fusion. The combination of increased membrane area and activated CR3 specifically equips MGCs to engulf large complement-coated targets. Moreover, we demonstrate these features in vivo in the recently described complement-dependent therapeutic elimination of systemic amyloid deposits by MGCs. MGCs are evidently more than the sum of their macrophage parts. Graphical Abstract Highlights • MGCs are specialized for phagocytosis of large and complement-opsonized particles • MGCs show extensive membrane ruffles containing pre-activated complement receptor 3 • Membrane ruffles provide excess membrane for ingestion of large materials • MGCs eliminate systemic amyloid deposits after immunotherapeutic targeting Macrophage-derived multinucleated giant cells (MGCs) form in diverse chronic inflammatory diseases, but their functional role remains unclear. Milde et al. show that MGCs are specialized for complement-mediated phagocytosis and destruction of large targets and demonstrate their key role in the therapeutic elimination of the pathogenic amyloid deposits in systemic amyloidosis. |
| Databáze: | OpenAIRE |
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