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

Milde, R; Ritter, J; Tennent, GA; Loesch, A; Martinez, FO; Gordon, S; Pepys, MB; ... Helming, L; + view all (2015) Multinucleated Giant Cells Are Specialized for Complement-Mediated Phagocytosis and Large Target Destruction. Cell Reports , 13 (9) pp. 1937-1948. 10.1016/j.celrep.2015.10.065. Green open access

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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.

Type: Article
Title: Multinucleated Giant Cells Are Specialized for Complement-Mediated Phagocytosis and Large Target Destruction
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2015.10.065
Publisher version: http://dx.doi.org/10.1016/j.celrep.2015.10.065
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1474620
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