细胞凋亡
缺血
心肌再灌注损伤
再灌注损伤
医学
内科学
心脏病学
化学
生物化学
作者
Fang‐Yang Huang,Jialiang Zhang,Hao Zhang,Tianyi Qu,Yan Wang,Kexin Jiang,Yutong Liu,Yuanning Xu,Mao Chen,Li Chen
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2024-02-22
卷期号:9 (4)
标识
DOI:10.1172/jci.insight.167201
摘要
A robust sterile inflammation underlies myocardial ischemia and reperfusion injury (MIRI). Several subsets of B-cells possess the immune-regulatory capacity that limits tissue damage, yet the role of B-cells in MIRI remains elusive. Here, we sought to elucidate the contribution of B-cells to the MIRI by transient ligation of the left anterior descending in the B-cell depleted or deficient mice. Following ischemia and reperfusion (I/R), regulatory B-cells are rapidly recruited to the heart. B-cell-depleted or deficient mice exhibited exacerbated tissue damage, adverse cardiac remodeling, and an augmented inflammatory response after I/R. Rescue and chimeric experiments indicated that the cardioprotective effect of B-cells was not solely dependent on IL10. Coculture experiments demonstrated that B-cells induced neutrophil apoptosis through contact-dependent interaction, subsequently promoting reparative macrophage polarization by facilitating the phagocytosis of neutrophils by macrophages. The in-vivo cardioprotective effect of B-cells was absent in absence of neutrophils after I/R. Mechanistically, ligand-receptor imputation identified FCER2A as a potential mediator of interactions between B-cells and neutrophils. Blocking FCER2A on B-cells resulted in a reduction in the percentage of apoptotic neutrophils, contributing to the deterioration of cardiac remodeling. Our findings unveil a potential cardioprotective role of B-cells in myocardial I/R through mechanisms involving FCER2A, neutrophil, and macrophage.
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