@article{547c7ab8ab0f4bdeb784943373d86cdc,
title = "Multinucleated Giant Cells Are Specialized for Complement-Mediated Phagocytosis and Large Target Destruction",
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.",
author = "Ronny Milde and Julia Ritter and Tennent, {Glenys A.} and Andrzej Loesch and Martinez, {Fernando O.} and Siamon Gordon and Pepys, {Mark B.} and Admar Verschoor and Laura Helming",
note = "Funding Information: We thank Dirk Busch, Patrick R{\"a}mer (both Technische Universit{\"a}t M{\"u}nchen), and Falk Nimmerjahn (Universit{\"a}t Erlangen-Nuernberg) for helpful comments on the manuscript, reagents, and/or experimental advice and Vanessa Landtwing (University of Zurich) for assistance with 3D visualizations. Christie Ballantyne (Baylor College of Medicine) kindly shared Itgax- knockout mice. We thank Karl Bodin, Melvyn Kahan, and Janet Gilbertson (University College London) for in vivo experiments in anti-SAP-treated mice and routine histology. This work was funded by the German Research Foundation (DFG) with grants HE 5190/3-1 to L.H. and SFB 914 (B4) to A.V. and the UK Medical Research Council Programme and Project grants to M.B.P. and G.A.T. We gratefully acknowledge support by the Technische Universit{\"a}t M{\"u}nchen Graduate School and the Wolfson Foundation at University College London. Publisher Copyright: {\textcopyright} 2015 The Authors. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",
year = "2015",
month = dec,
day = "1",
doi = "10.1016/j.celrep.2015.10.065",
language = "English",
volume = "13",
pages = "1937--1948",
journal = "Cell Reports",
issn = "2211-1247",
number = "9",
}
