Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723964.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Myocardial healing requires Reg3beta-dependent accumulation of macrophages in the ischemic heart
Authors:Lorchner, H.; Poling, J.; Gajawada, P.; Hou, Y.; Polyakova, V.; Kostin, S.; Adrian-Segarra, J. M.; Boettger, T.; Wietelmann, A.; Warnecke, H.; Richter, M.; Kubin, T.; Braun, T.
Date of Publication (YYYY-MM-DD):2015-04
Title of Journal:Nat Med
Volume:21
Issue / Number:4
Start Page:353
End Page:362
Audience:Not Specified
Abstract / Description:Cardiac healing after myocardial ischemia depends on the recruitment and local expansion of myeloid cells, particularly macrophages. Here we identify Reg3beta as an essential regulator of macrophage trafficking to the damaged heart. Using mass spectrometry-based secretome analysis, we found that dedifferentiating cardiomyocytes release Reg3beta in response to the cytokine OSM, which signals through Jak1 and Stat3. Loss of Reg3beta led to a large decrease in the number of macrophages in the ischemic heart, accompanied by increased ventricular dilatation and insufficient removal of neutrophils. This defect in neutrophil removal in turn caused enhanced matrix degradation, delayed collagen deposition and increased susceptibility to cardiac rupture. Our data indicate that OSM, acting through distinct intracellular pathways, regulates both cardiomyocyte dedifferentiation and cardiomyocyte-dependent regulation of macrophage trafficking. Release of OSM from infiltrating neutrophils and macrophages initiates a positive feedback loop in which OSM-induced production of Reg3beta in cardiomyocytes attracts additional OSM-secreting macrophages. The activity of the feedback loop controls the degree of macrophage accumulation in the heart, which is instrumental in myocardial healing.
Free Keywords:Animals; Antigens, Neoplasm/genetics/*metabolism; Collagen/metabolism; Electrophoresis, Gel, Two-Dimensional; Female; Heart/physiology; Heart Ventricles/metabolism; Inflammation; Interleukin-6/metabolism; Lectins, C-Type/genetics/*metabolism; Macrophages/cytology/*metabolism; Male; Mice; Mice, Transgenic; Myocardial Ischemia/*pathology; Myocardium/*pathology; Myocytes, Cardiac/metabolism; Oncostatin M/*metabolism; Proteins/genetics/*metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction; Tumor Markers, Biological/genetics/*metabolism
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:1] Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. [2] Department of Cardiac Surgery, Schuchtermann-Clinic, Bad Rothenfelde, Germany. Department of Cardiac Surgery, Schuchtermann-Clinic, Bad Rothenfelde, Germany. Department of Cardiac Surgery, Kerckhoff-Klinik, Bad Nauheim, Germany.
Identifiers:ISSN:1546-170X (Electronic) 1078-8956 (Linking) %R 10.1038/nm.3816
URL:http://www.ncbi.nlm.nih.gov/pubmed/25751817
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.