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PMID: 18957693 Published · epublish English Journal Article

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

Science signaling ·Vol. 1 ·No. 43 ·2008-10-28 ·Pages ra11

Helming L, Tomasello E, Kyriakides TR, Martinez FO, Takai T, Gordon S, Vivier E

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing/metabolism,physiology Animals Cell Fusion Cytokines/pharmacology Gene Expression Regulation Inflammation/pathology Intracellular Signaling Peptides and Proteins/physiology Macrophages/pathology Membrane Glycoproteins/physiology Mice Mice, Inbred C57BL Protein-Tyrosine Kinases/physiology Receptors, Immunologic/physiology Signal Transduction/genetics Syk Kinase
Chemicals
Adaptor Proteins, Signal Transducing Cytokines Intracellular Signaling Peptides and Proteins Membrane Glycoproteins Receptors, Immunologic Trem2 protein, mouse Tyrobp protein, mouse Protein-Tyrosine Kinases Syk Kinase Syk protein, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Helming Laura
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Tomasello Elena
Kyriakides Themis R
Martinez Fernando O
Takai Toshiyuki
Gordon Siamon
Vivier Eric
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Article Info
Journal
Science signaling
Abbr.
Sci Signal
ISSN
1937-9145
DOI
10.1126/scisignal.1159665
Published
2008-10-28
Epub
2008-00-28
Pages
ra11
Language
English
Region
United States
NLM ID
101465400
PMCID
PMC2673960
Subset
IM
Grants
Medical Research Council · G0600727 · United Kingdom
NIGMS NIH HHS · R01 GM072194 · United States
NIGMS NIH HHS · R01 GM072194-04 · United States
External Links
PubMed source DOI: 10.1126/scisignal.1159665 PMC Full Text View journal details
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