TY - JOUR
T1 - Efferocytosis and outside-in signaling by cardiac phagocytes. Links to repair, cellular programming, and intercellular crosstalk in heart
AU - DeBerge, Matthew
AU - Zhang, Shuang
AU - Glinton, Kristofor
AU - Grigoryeva, Luba
AU - Hussein, Islam
AU - Vorovich, Esther
AU - Ho, Karen
AU - Luo, Xunrong
AU - Thorp, Edward B.
N1 - Publisher Copyright:
© 2017 DeBerge, Zhang, Glinton, Grigoryeva, Hussein, Vorovich, Ho, Luo and Thorp.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
KW - Cardiomyocyte
KW - Efferocytosis
KW - Heart
KW - Macrophage
KW - Phagocytosis
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UR - http://www.scopus.com/inward/citedby.url?scp=85032722598&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.01428
DO - 10.3389/fimmu.2017.01428
M3 - Review article
C2 - 29163503
AN - SCOPUS:85032722598
SN - 1664-3224
VL - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - NOV
M1 - 1428
ER -