Myocardial infarction (MI) elicits massive inflammatory leukocyte recruitment to the heart. Here, we hypothesized that excessive leukocyte invasion leads to heart failure and death during acute myocardial ischemia. We found that shortly and transiently after onset of ischemia, human and mouse cardiac fibroblasts produce granulocyte/macrophage colony-stimulating factor (GM-CSF) that acts locally and distally to generate and recruit inflammatory and proteolytic cells. In the heart, fibroblast-derived GM-CSF alerts its neighboring myeloid cells to attract neutrophils and monocytes. The growth factor also reaches the bone marrow, where it stimulates a distinct myeloid-biased progenitor subset. Consequently, hearts of mice deficient in either GM-CSF or its receptor recruit fewer leukocytes and function relatively well, whereas mice producing GM-CSF can succumb from left ventricular rupture, a complication mitigated by anti–GM-CSF therapy. These results identify GM-CSF as both a key contributor to the pathogenesis of MI and a potential therapeutic target, bolstering the idea that GM-CSF is a major orchestrator of the leukocyte supply chain during inflammation.

心肌梗塞（MI）引发大量炎症性白细胞募集到心脏。在这里，我们假设过度的白细胞入侵会导致急性心肌缺血期间的心力衰竭和死亡。我们发现缺血发作后不久，人类和小鼠的心脏成纤维细胞会产生粒细胞/巨噬细胞集落刺激因子（GM-CSF），在局部和远端产生并募集炎症和蛋白水解细胞。在心脏中，成纤维细胞衍生的GM-CSF会提醒其邻近的髓样细胞吸引中性粒细胞和单核细胞。生长因子也到达骨髓，在骨髓中刺激了一个独特的由髓样偏向的祖细胞。因此，缺乏GM-CSF或其受体的小鼠心脏募集的白细胞较少，并且功能相对较好，而产生GM-CSF的小鼠可因左室破裂而屈服，这种并发症可通过抗GM-CSF疗法缓解。这些结果确定了GM-CSF既是MI发病机理的关键贡献者，又是潜在的治疗靶标，从而支持了GM-CSF是炎症过程中白细胞供应链的主要协调者的想法。