Essential role of DAP12 signaling in macrophage programming into a fusion-competent state.

Journal article

Multinucleated giant cells, formed by fusion of macrophages, are a hallmark of granulomatous inflammation. With a genetic approach, we show that signaling through the adaptor protein DAP12 (DNAX activating protein of 12 kD), its associated receptor triggering receptor expressed by myeloid cells 2 (TREM-2), and the downstream protein tyrosine kinase Syk is required for the cytokine-induced formation of giant cells and that overexpression of DAP12 potentiates macrophage fusion. We also present evidence that DAP12 is a general macrophage fusion regulator and is involved in modulating the expression of several macrophage-associated genes, including those encoding known mediators of macrophage fusion, such as DC-STAMP and Cadherin 1. Thus, DAP12 is involved in programming of macrophages through the regulation of gene and protein expression to induce a fusion-competent state.

Authors: Helming, L; Tomasello, E; Kyriakides, T; Martinez, F; Takai, T

• Publication status: Published
• Journal: Science signaling
• Volume: 1
• Issue: 43
• Pages: ra11
• Publication date: 2008-01-01
• DOI: 10.1126/scisignal.1159665
• EISSN: 1937-9145
• ISSN: 1937-9145
• Language: English
• Keywords: Macrophages; Cell Fusion; Cytokines; Protein-Tyrosine Kinases; Mice, Inbred C57BL; Mice; Adaptor Proteins, Signal Transducing; Membrane Glycoproteins; Signal Transduction; Animals; Inflammation; Gene Expression Regulation; Receptors, Immunologic; Intracellular Signaling Peptides and Proteins