Efferocytosis and outside-in signaling by cardiac phagocytes. Links to repair, cellular programming, and intercellular crosstalk in heart

Matthew DeBerge, Shuang Zhang, Kristofor Glinton, Luba Grigoryeva, Islam Hussein, Esther Elizabeth Vorovich, Karen J Ho, Xunrong Luo, Edward Benjamin Thorp*

*Corresponding author for this work

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

Phagocytic sensing and engulfment of dying cells and extracellular bodies initiate an intracellular signaling cascade within the phagocyte that can polarize cellular function and promote communication with neighboring non-phagocytes. Accumulating evidence links phagocytic signaling in the heart to cardiac development, adult myocardial homeostasis, and the resolution of cardiac inflammation of infectious, ischemic, and aging-associated etiology. Phagocytic clearance in the heart may be carried out by professional phagocytes, such as macrophages, and non-professional cells, including myofibrolasts and potentially epithelial cells. During cardiac development, phagocytosis initiates growth cues for early cardiac morphogenesis. In diseases of aging, including myocardial infarction, heightened levels of cell death require efficient phagocytic debridement to salvage further loss of terminally differentiated adult cardiomyocytes. Additional risk factors, including insulin resistance and other systemic risk factors, contribute to inefficient phagocytosis, altered phagocytic signaling, and delayed cardiac inflammation resolution. Under such conditions, inflammatory presentation of myocardial antigen may lead to autoimmunity and even possible rejection of transplanted heart allografts. Increased understanding of these basic mechanisms offers therapeutic opportunities.

Original languageEnglish (US)
Article number1428
JournalFrontiers in immunology
Volume8
Issue numberNOV
DOIs
StatePublished - Nov 1 2017

Keywords

  • Cardiomyocyte
  • Efferocytosis
  • Heart
  • Macrophage
  • Phagocytosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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