دورية أكاديمية
أعرض في EDS

MerTK Cleavage on Resident Cardiac Macrophages Compromises Repair After Myocardial Ischemia Reperfusion Injury.

التفاصيل البيبلوغرافية
العنوان: MerTK Cleavage on Resident Cardiac Macrophages Compromises Repair After Myocardial Ischemia Reperfusion Injury.
المؤلفون: DeBerge M; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Yeap XY; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Dehn S; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Zhang S; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Grigoryeva L; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Misener S; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Procissi D; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Zhou X; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Lee DC; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Muller WA; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Luo X; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Rothlin C; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Tabas I; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.)., Thorp EB; From the Department of Pathology and Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.D., X.Y.Y., S.D., S.Z., L.G., S.M., D.P., X.Z., D.C.Le., W.A.M., X.L., E.B.T.); Division of Molecular Medicine at Columbia University, New York (I.T.); and Department of Immunobiology, School of Medicine, Yale University (C.R.). ebthorp@northwestern.edu.
المصدر: Circulation research [Circ Res] 2017 Sep 29; Vol. 121 (8), pp. 930-940. Date of Electronic Publication: 2017 Aug 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0047103 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4571 (Electronic) Linking ISSN: 00097330 NLM ISO Abbreviation: Circ Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Baltimore, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Md. Grune & Stratton.
مواضيع طبية MeSH: Macrophages/*enzymology , Myocardial Reperfusion Injury/*enzymology , Myocardium/*enzymology , Proto-Oncogene Proteins/*metabolism , Receptor Protein-Tyrosine Kinases/*metabolism , ST Elevation Myocardial Infarction/*enzymology, Animals ; Apoptosis ; Cytokines/immunology ; Cytokines/metabolism ; Disease Models, Animal ; Female ; Genetic Predisposition to Disease ; Histocompatibility Antigens Class II/immunology ; Histocompatibility Antigens Class II/metabolism ; Humans ; Immunity, Innate ; Macrophages/immunology ; Macrophages/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Monocytes/enzymology ; Monocytes/immunology ; Myocardial Reperfusion Injury/immunology ; Myocardial Reperfusion Injury/pathology ; Myocardial Reperfusion Injury/physiopathology ; Myocardium/immunology ; Myocardium/pathology ; Phagocytosis ; Phenotype ; Proteolysis ; Proto-Oncogene Proteins/deficiency ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/immunology ; Receptor Protein-Tyrosine Kinases/deficiency ; Receptor Protein-Tyrosine Kinases/genetics ; Receptor Protein-Tyrosine Kinases/immunology ; Receptors, CCR2/genetics ; Receptors, CCR2/immunology ; Receptors, CCR2/metabolism ; ST Elevation Myocardial Infarction/immunology ; ST Elevation Myocardial Infarction/pathology ; ST Elevation Myocardial Infarction/physiopathology ; Signal Transduction ; Time Factors ; c-Mer Tyrosine Kinase
مستخلص: Rationale: Clinical benefits of reperfusion after myocardial infarction are offset by maladaptive innate immune cell function, and therapeutic interventions are lacking.
Objective: We sought to test the significance of phagocytic clearance by resident and recruited phagocytes after myocardial ischemia reperfusion.
Methods and Results: In humans, we discovered that clinical reperfusion after myocardial infarction led to significant elevation of the soluble form of MerTK (myeloid-epithelial-reproductive tyrosine kinase; ie, soluble MER), a critical biomarker of compromised phagocytosis by innate macrophages. In reperfused mice, macrophage Mertk deficiency led to decreased cardiac wound debridement, increased infarct size, and depressed cardiac function, newly implicating MerTK in cardiac repair after myocardial ischemia reperfusion. More notably, Mertk(CR ) mice, which are resistant to cleavage, showed significantly reduced infarct sizes and improved systolic function. In contrast to other cardiac phagocyte subsets, resident cardiac MHCII LO CCR2 - (major histocompatibility complex II/C-C motif chemokine receptor type 2) macrophages expressed higher levels of MerTK and, when exposed to apoptotic cells, secreted proreparative cytokines, including transforming growth factor-β. Mertk deficiency compromised the accumulation of MHCII LO phagocytes, and this was rescued in Mertk(CR ) mice. Interestingly, blockade of CCR2-dependent monocyte infiltration into the heart reduced soluble MER levels post-ischemia reperfusion.
Conclusions: Our data implicate monocyte-induced MerTK cleavage on proreparative MHCII LO cardiac macrophages as a novel contributor and therapeutic target of reperfusion injury.
(© 2017 American Heart Association, Inc.)
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معلومات مُعتمدة: R01 HL064774 United States HL NHLBI NIH HHS; R01 HL046849 United States HL NHLBI NIH HHS; F32 HL127958 United States HL NHLBI NIH HHS; R25 GM079300 United States GM NIGMS NIH HHS; R01 HL122309 United States HL NHLBI NIH HHS; T32 GM008061 United States GM NIGMS NIH HHS; R01 HL132412 United States HL NHLBI NIH HHS; UL1 TR001422 United States TR NCATS NIH HHS; R01 HL127464 United States HL NHLBI NIH HHS; R01 HL075662 United States HL NHLBI NIH HHS; R01 AI089824 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: efferocytosis; inflammation; ischemia reperfusion injury; macrophage; phagocytosis
المشرفين على المادة: 0 (Ccr2 protein, mouse)
0 (Cytokines)
0 (Histocompatibility Antigens Class II)
0 (Proto-Oncogene Proteins)
0 (Receptors, CCR2)
EC 2.7.10.1 (MERTK protein, human)
EC 2.7.10.1 (Mertk protein, mouse)
EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
EC 2.7.10.1 (c-Mer Tyrosine Kinase)
تواريخ الأحداث: Date Created: 20170831 Date Completed: 20171010 Latest Revision: 20190111
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5623080
DOI: 10.1161/CIRCRESAHA.117.311327
PMID: 28851810
قاعدة البيانات: MEDLINE
الوصف
تدمد:1524-4571
DOI:10.1161/CIRCRESAHA.117.311327