期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 131, 期 13, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI136778
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资金
- German Research Foundation (DFG) [LE 2530/51, SFB 850, SFB160]
- Leducq Foundation
- German Cardiac Society (DGK)
- German Federal Ministry of Education and Research within the Medical Informatics Funding Scheme (MIRACUM) [FKZ 01ZZ1606B]
- [FKZ 01ZX1708F]
The study show that basophils play a crucial role in promoting tissue repair after myocardial infarction by increasing levels of IL-4 and IL-13 in the heart. Depletion of basophils leads to an increase in inflammatory response, scar thinning, and deterioration of cardiac function post-MI.
The inflammatory response after myocardial infarction (MI) is a precisely regulated process that greatly affects subsequent remodeling. Here, we show that basophil granulocytes infiltrated infarcted murine hearts, with a peak occurring between days 3 and 7. Antibody-mediated and genetic depletion of basophils deteriorated cardiac function and resulted in enhanced scar thinning after MI. Mechanistically, we found that basophil depletion was associated with a shift from reparative Ly6C(lo) macrophages toward increased numbers of inflammatory Ly6C(hi) monocytes in the infarcted myocardium. Restoration of basophils in basophil-deficient mice by adoptive transfer reversed this proinflammatory phenotype. Cellular alterations in the absence of basophils were accompanied by lower cardiac levels of IL-4 and IL-13, two major cytokines secreted by basophils. Mice with basophil-specific IL-4/IL-13 deficiency exhibited a similarly altered myeloid response with an increased fraction of Ly6C(hi) monocytes and aggravated cardiac function after MI. In contrast, IL-4 induction in basophils via administration of the glycoprotein IPSE/alpha-1 led to improved post-MI healing. These results in mice were corroborated by the finding that initially low counts of blood basophils in patients with acute MI were associated with a worse cardiac outcome after 1 year, characterized by a larger scar size. In conclusion, we show that basophils promoted tissue repair after MI by increasing cardiac IL-4 and IL-13 levels.
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