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Publication : Multinucleated Giant Cells Are Specialized for Complement-Mediated Phagocytosis and Large Target Destruction.

First Author  Milde R Year  2015
Journal  Cell Rep Volume  13
Issue  9 Pages  1937-48
PubMed ID  26628365 Mgi Jnum  J:266025
Mgi Id  MGI:6208770 Doi  10.1016/j.celrep.2015.10.065
Citation  Milde R, et al. (2015) Multinucleated Giant Cells Are Specialized for Complement-Mediated Phagocytosis and Large Target Destruction. Cell Rep 13(9):1937-48
abstractText  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.
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