1. Multinucleated Giant Cells Are Specialized for Complement-Mediated Phagocytosis and Large Target Destruction.
- Author
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Milde R, Ritter J, Tennent GA, Loesch A, Martinez FO, Gordon S, Pepys MB, Verschoor A, and Helming L
- Subjects
- Amyloid metabolism, Animals, Bone Marrow Cells cytology, Bone Marrow Cells drug effects, Bone Marrow Cells metabolism, CD11c Antigen metabolism, CD18 Antigens metabolism, Complement C3 deficiency, Complement C3 genetics, Complement C3 metabolism, Cricetinae, Giant Cells immunology, Humans, Integrin alphaXbeta2 metabolism, Macrophage Colony-Stimulating Factor pharmacology, Macrophages cytology, Macrophages drug effects, Macrophages metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Rats, Receptors, IgG metabolism, Tetradecanoylphorbol Acetate pharmacology, Up-Regulation drug effects, Giant Cells metabolism, Interleukin-4 pharmacology, Phagocytosis drug effects
- Abstract
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., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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