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

• DOI: 10.1084/jem.20170689
• Publication Date: 2017-10-04T14:10:10Z
• Authors: Atsushi Anzai; Jennifer L. Choi; Shun He; Ashley M. Fenn; Manfred Nairz; Sara Rattik; Cameron S. McAlpine; John E. Mindur; Christopher T. Chan; Yoshiko Iwamoto; Benoit Tricot; Gregory R. Wojtki...; Ralph Weissleder; Peter Libby; Matthias Nahrendorf; James R. Stone; Burkhard Becher; Filip K. Swirski
• Keywords: Male; 0301 basic medicine; Neutrophils; Myocardial Infarction; 610; 610 Medicine & health; Mice, Transgenic; 10263 Institute of Experimental Immunology; Article; Monocytes; Cytokine Receptor Common beta Subunit; 03 medical and health sciences; Bone Marrow; 616; Leukocytes; Animals; Humans; Myeloid Cells; Research Articles; Inflammation; Mice, Knockout; 2403 Immunology; 0303 health sciences; Granulocyte-Macrophage Colony-Stimulating Factor; Flow Cytometry; Survival Analysis; 3. Good health; Mice, Inbred C57BL; 2723 Immunology and Allergy; 570 Life sciences; biology; Chemokines

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