Identification of Pathogenic Cardiac CD11c+ Macrophages in Nod1-Mediated Acute Coronary Arteritis

Yoshitomo Motomura, Shunsuke Kanno, Kenichi Asano, Masato Tanaka, Yutaka Hasegawa, Hideki Katagiri, Takashi Saito, Hiromitsu Hara, Hisanori Nishio, Toshiro Hara, Sho Yamasaki

研究成果: ジャーナルへの寄稿学術誌査読

30 被引用数 (Scopus)

抄録

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+Ly6Chi 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 Ly6Chi 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.

本文言語英語
ページ(範囲)1423-1433
ページ数11
ジャーナルArteriosclerosis, thrombosis, and vascular biology
35
6
DOI
出版ステータス出版済み - 6月 27 2015

!!!All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学

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