Identification of Pathogenic Cardiac CD11c+ Macrophages in Nod1-Mediated Acute Coronary Arteritis. Issue 6 (June 2015)

• Record Type: Journal Article
• Authors: Motomura, Yoshitomo; Kanno, Shunsuke; Asano, Kenichi; Tanaka, Masato; Hasegawa, Yutaka; Katagiri, Hideki; Saito, Takashi; Hara, Hiromitsu; Nishio, Hisanori; Hara, Toshiro; Yamasaki, Sho
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 35:Issue 6(2015)
• Publication Date: 2015-06
• Subjects: Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.114.304846
• Languages: English
• ISSNs: 1079-5642

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective—</title> <p>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.</p> </sec> <sec> <title>Approach and Results—</title> <p>We found that CD11c<sup>+</sup>MHC class II<sup>+</sup> cells accumulated in the heart of FK565-treated mice before arteritis development. Morphological features and gene expression signatures of the cardiac CD11c<sup>+</sup>MHC class II<sup>+</sup> cells suggested that this population is closely related to macrophages, and thus, we designated them cardiac CD11c<sup>+</sup> macrophages. Nod1 in nonhematopoietic cells, rather than hematopoietic cells, was required for the increase of cardiac CD11c<sup>+</sup> 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<sup>+</sup> macrophages, and subsequent coronary arteritis development. We also found that CCR2<sup>+</sup>Ly6C<sup>hi</sup> inflammatory monocytes in peripheral blood supplied precursors of cardiac CD11c<sup>+</sup> macrophages. CCR2-deficient mice or pertussis toxin–treated mice exhibited decreased numbers of cardiac CD11c<sup>+</sup> macrophages and reduced arteritis.</p> </sec> <sec> <title>Conclusions—</title> <p>These results suggest that Ly6C<sup>hi</sup> monocytes are recruited to FK565-activated endothelial cells to generate cardiac CD11c<sup>+</sup> macrophages, which play a pivotal role in the pathogenesis of acute coronary arteritis.</p> </sec> </abstract>