title: An abundant tissue macrophage population in the adult murine heart with a distinct alternatively-activated macrophage profile.
abstract: Cardiac tissue macrophages (cTMs) are a previously uncharacterised cell type that we have identified and characterise here as an abundant GFP(+) population within the adult Cx(3)cr1(GFP/+) knock-in mouse heart. They comprise the predominant myeloid cell population in the myocardium, and are found throughout myocardial interstitial spaces interacting directly with capillary endothelial cells and cardiomyocytes. Flow cytometry-based immunophenotyping shows that cTMs exhibit canonical macrophage markers. Gene expression analysis shows that cTMs (CD45(+)CD11b(+)GFP(+)) are distinct from mononuclear CD45(+)CD11b(+)GFP(+) cells sorted from the spleen and brain of adult Cx(3)cr1(GFP/+) mice. Gene expression profiling reveals that cTMs closely resemble alternatively-activated anti-inflammatory M2 macrophages, expressing a number of M2 markers, including Mrc1, CD163, and Lyve-1. While cTMs perform normal tissue macrophage homeostatic functions, they also exhibit a distinct phenotype, involving secretion of salutary factors (including IGF-1) and immune modulation. In summary, the characterisation of cTMs at the cellular and molecular level defines a potentially important role for these cells in cardiac homeostasis.
authors.affiliation: European Molecular Biology Laboratory, Mouse Biology Unit, Monterotondo, Rome, Italy. alex.pinto@monash.edu
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Pinto
authors.forename: Rosa
authors.initials: R
authors.lastname: Paolicelli
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Salimova
authors.forename: Janko
authors.initials: J
authors.lastname: Gospocic
authors.forename: Esfir
authors.initials: E
authors.lastname: Slonimsky
authors.forename: Daniel
authors.initials: D
authors.lastname: Bilbao-Cortes
authors.forename: James W
authors.initials: JW
authors.lastname: Godwin
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001921:Brain / Q000166:cytology / Q000378:metabolism; D039481:CD11b Antigen / Q000096:biosynthesis; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis; D006706:Homeostasis / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D039481:CD11b Antigen; D006023:Glycoproteins; D007334:Insulin-Like Growth Factor I; D017493:Leukocyte Common Antigens; D026901:Membrane Transport Proteins; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C492273:LYVE1 protein, mouse; C519530:insulin-like growth factor-1, mouse; C516770:Ptprc protein, mouse