First Author | Helming L | Year | 2008 |
Journal | Sci Signal | Volume | 1 |
Issue | 43 | Pages | ra11 |
PubMed ID | 18957693 | Mgi Jnum | J:258167 |
Mgi Id | MGI:6142486 | Doi | 10.1126/scisignal.1159665 |
Citation | Helming L, et al. (2008) Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. Sci Signal 1(43):ra11 |
abstractText | 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. |