| First Author | Motomura Y | Year | 2015 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 35 |
| Issue | 6 | Pages | 1423-33 |
| PubMed ID | 25838430 | Mgi Jnum | J:241622 |
| Mgi Id | MGI:5903191 | Doi | 10.1161/ATVBAHA.114.304846 |
| Citation | Motomura Y, et al. (2015) Identification of Pathogenic Cardiac CD11c+ Macrophages in Nod1-Mediated Acute Coronary Arteritis. Arterioscler Thromb Vasc Biol 35(6):1423-33 |
| abstractText | OBJECTIVE: Nod1 is an intracellular pattern recognition receptor for bacterial peptidoglycan fragments. We previously reported that a synthetic Nod1 ligand, FK565, induced acute coronary arteritis in mice similar to that of Kawasaki disease. However, the molecular mechanisms underlying this characteristic inflammation have remained elusive. APPROACH AND RESULTS: We found that CD11c(+)MHC class II(+) cells accumulated in the heart of FK565-treated mice before arteritis development. Morphological features and gene expression signatures of the cardiac CD11c(+)MHC class II(+) cells suggested that this population is closely related to macrophages, and thus, we designated them cardiac CD11c(+) macrophages. Nod1 in nonhematopoietic cells, rather than hematopoietic cells, was required for the increase of cardiac CD11c(+) macrophages and arteritis development. Among nonhematopoietic cells, cardiac endothelial cells produced a large amount of chemokines in response to FK565. Endothelial cell-specific blockade of Nod1 signaling suppressed FK565-induced expression of these chemokines, accumulation of cardiac CD11c(+) macrophages, and subsequent coronary arteritis development. We also found that CCR2(+)Ly6C(hi) inflammatory monocytes in peripheral blood supplied precursors of cardiac CD11c(+) macrophages. CCR2-deficient mice or pertussis toxin-treated mice exhibited decreased numbers of cardiac CD11c(+) macrophages and reduced arteritis. CONCLUSIONS: These results suggest that Ly6C(hi) monocytes are recruited to FK565-activated endothelial cells to generate cardiac CD11c(+) macrophages, which play a pivotal role in the pathogenesis of acute coronary arteritis. |
