B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.
B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.
复制标题
作者：
急性心肌梗塞是一种严重的缺血性疾病，可导致心力衰竭和猝死。在这里，我们发现，小鼠急性心肌梗死后，成熟的 B 淋巴细胞选择性产生 Ccl7 并诱导 Ly6Chi 单核细胞动员和募集到心脏，导致组织损伤加剧和心肌功能恶化。成熟 B 淋巴细胞的遗传（Baff 受体缺陷）或抗体介导的（CD20 或 Baff 特异性抗体）耗竭阻碍了 Ccl7 的产生和单核细胞的动员，限制了心肌损伤并改善了心脏功能。这些效应在 B 细胞选择性 Ccl7 缺陷的小鼠身上得到了重现。我们还表明，急性心肌梗塞患者中 CCL7 和 BAFF 的高循环浓度预示着死亡或复发性心肌梗塞的风险增加。这项工作确定了急性心肌缺血后成熟 B 淋巴细胞和单核细胞之间的重要相互作用，并确定了急性心肌梗死的新治疗靶点。
Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction.
登录
查看更多内容
DOI：
10.1084/jem.20101715
发表时间：
2011-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kelly-Scumpia KM;Scumpia PO;Weinstein JS;Delano MJ;Cuenca AG;Nacionales DC;Wynn JL;Lee PY;Kumagai Y;Efron PA;Akira S;Wasserfall C;Atkinson MA;Moldawer LL
通讯作者：
Moldawer LL
影响因子：
4.4
作者：
Kyaw, Tin;Tay, Christopher;Toh, Ban-Hock
通讯作者：
Toh, Ban-Hock
影响因子：
4.4
作者：
Hamaguchi, Y;Uchida, J;Tedder, TF
通讯作者：
Tedder, TF
影响因子：
11.3
作者：
Goodchild, Traci T.;Robinson, Keith A.;Chronos, Nicolas A. F.
通讯作者：
Chronos, Nicolas A. F.
影响因子：
37.8
作者：
Salio, Monica;Chimenti, Stefano;Mantovani, Alberto
通讯作者：
Mantovani, Alberto