The infarcted myocardium solicits GM-CSF for the detrimental oversupply of inflammatory leukocytes

J Exp Med. 2017 Nov 6;214(11):3293-3310. doi: 10.1084/jem.20170689. Epub 2017 Oct 4.


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.

MeSH terms

  • Animals
  • Bone Marrow / metabolism
  • Chemokines / metabolism
  • Cytokine Receptor Common beta Subunit / genetics
  • Cytokine Receptor Common beta Subunit / metabolism
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Leukocytes / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Monocytes / metabolism
  • Myeloid Cells / metabolism
  • Myocardial Infarction / metabolism*
  • Neutrophils / metabolism
  • Survival Analysis


  • Chemokines
  • Cytokine Receptor Common beta Subunit
  • Granulocyte-Macrophage Colony-Stimulating Factor