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

Ronny Milde, Julia Ritter, Glenys A. Tennent, Andrzej Loesch, Fernando O. Martinez, Siamon Gordon, Mark B. Pepys*, Admar Verschoor, Laura Helming

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

106 Scopus citations

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.

Original languageEnglish
Pages (from-to)1937-1948
Number of pages12
JournalCell Reports
Volume13
Issue number9
DOIs
StatePublished - 01 12 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 The Authors.

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