1] Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, Paris, France. [2] Université Paris-Descartes, Paris, France. [3].
Nat Med. 2013 Oct;19(10):1273-80. doi: 10.1038/nm.3284. Epub 2013 Sep 15.
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 Ly6C(hi) 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.
急性心肌梗死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，在小鼠急性心肌梗死后，成熟 B 淋巴细胞选择性地产生 Ccl7，并诱导 Ly6C(hi)单核细胞动员和募集到心脏，导致组织损伤加重和心肌功能恶化。通过遗传（Baff 受体缺陷）或抗体介导（CD20 或 Baff 特异性抗体）耗竭成熟 B 淋巴细胞，可阻碍 Ccl7 的产生和单核细胞的动员，从而限制心肌损伤并改善心脏功能。在 B 细胞选择性 Ccl7 缺陷的小鼠中也观察到了这些效应。我们还发现，急性心肌梗死后患者循环中 CCL7 和 BAFF 的浓度升高预示着死亡或再次发生心肌梗死的风险增加。这项工作确定了急性心肌缺血后成熟 B 淋巴细胞与单核细胞之间的关键相互作用，并为急性心肌梗死确定了新的治疗靶点。
