title: Tracking Monocyte Recruitment and Macrophage Accumulation in Atherosclerotic Plaque Progression Using a Novel hCD68GFP/ApoE-/- Reporter Mouse-Brief Report.
abstract: To create a model of atherosclerosis using green fluorescent protein (GFP)-targeted monocytes/macrophages, allowing analysis of both endogenous GFP+and adoptively transferred GFP+myeloid cells in arterial inflammation. APPROACH AND RESULTS: hCD68GFP reporter mice were crossed with ApoE-/-mice. Expression of GFP was localized to macrophages in atherosclerotic plaques and in angiotensin II-induced aortic aneurysms and correlated with galectin 3 and mCD68 expression. Flow cytometry confirmed GFP+expression in CD11b+/CD64+, CD11c+/MHC-IIHI, and CD11b+/F4/80+myeloid cells. Adoptive transfer of GFP+monocytes demonstrated monocyte recruitment to both adventitia and atherosclerotic plaque, throughout the aortic root, within 72 hours. We demonstrated the biological utility of hCD68GFP monocytes by comparing the recruitment of wild-type and CCR2-/-monocytes to sites of inflammation.
  
  
  
  hCD68GFP/ApoE-/-mice provide a new approach to study macrophage accumulation in atherosclerotic plaque progression and to identify cells recruited from adoptively transferred monocytes.
authors.affiliation: From the Division of Cardiovascular Medicine, British Heart Foundation Centre for Research Excellence, Radcliffe Department of Medicine, John Radcliffe Hospital, United Kingdom (E.M., D.J., J.P., P.C., K.M.C.); Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom (E.M., J.P., P.C., K.M.C.); and Sir William Dunn School of Pathology, University of Oxford, United Kingdom (A.J.I., L.T., D.R.G.). eileen.mcneill@well.ox.ac.uk.
authors.forename: Eileen
authors.initials: E
authors.lastname: McNeill
authors.affiliation: From the Division of Cardiovascular Medicine, British Heart Foundation Centre for Research Excellence, Radcliffe Department of Medicine, John Radcliffe Hospital, United Kingdom (E.M., D.J., J.P., P.C., K.M.C.); Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom (E.M., J.P., P.C., K.M.C.); and Sir William Dunn School of Pathology, University of Oxford, United Kingdom (A.J.I., L.T., D.R.G.).
authors.forename: Asif J
authors.initials: AJ
authors.lastname: Iqbal
authors.affiliation: From the Division of Cardiovascular Medicine, British Heart Foundation Centre for Research Excellence, Radcliffe Department of Medicine, John Radcliffe Hospital, United Kingdom (E.M., D.J., J.P., P.C., K.M.C.); Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom (E.M., J.P., P.C., K.M.C.); and Sir William Dunn School of Pathology, University of Oxford, United Kingdom (A.J.I., L.T., D.R.G.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Jones
authors.affiliation: From the Division of Cardiovascular Medicine, British Heart Foundation Centre for Research Excellence, Radcliffe Department of Medicine, John Radcliffe Hospital, United Kingdom (E.M., D.J., J.P., P.C., K.M.C.); Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom (E.M., J.P., P.C., K.M.C.); and Sir William Dunn School of Pathology, University of Oxford, United Kingdom (A.J.I., L.T., D.R.G.).
authors.forename: Jyoti
authors.initials: J
authors.lastname: Patel
authors.affiliation: From the Division of Cardiovascular Medicine, British Heart Foundation Centre for Research Excellence, Radcliffe Department of Medicine, John Radcliffe Hospital, United Kingdom (E.M., D.J., J.P., P.C., K.M.C.); Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom (E.M., J.P., P.C., K.M.C.); and Sir William Dunn School of Pathology, University of Oxford, United Kingdom (A.J.I., L.T., D.R.G.).
authors.forename: Patricia
authors.initials: P
authors.lastname: Coutinho
authors.affiliation: From the Division of Cardiovascular Medicine, British Heart Foundation Centre for Research Excellence, Radcliffe Department of Medicine, John Radcliffe Hospital, United Kingdom (E.M., D.J., J.P., P.C., K.M.C.); Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom (E.M., J.P., P.C., K.M.C.); and Sir William Dunn School of Pathology, University of Oxford, United Kingdom (A.J.I., L.T., D.R.G.).
authors.forename: Lewis
authors.initials: L
authors.lastname: Taylor
authors.affiliation: From the Division of Cardiovascular Medicine, British Heart Foundation Centre for Research Excellence, Radcliffe Department of Medicine, John Radcliffe Hospital, United Kingdom (E.M., D.J., J.P., P.C., K.M.C.); Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom (E.M., J.P., P.C., K.M.C.); and Sir William Dunn School of Pathology, University of Oxford, United Kingdom (A.J.I., L.T., D.R.G.).
authors.forename: David R
authors.initials: DR
authors.lastname: Greaves
authors.affiliation: From the Division of Cardiovascular Medicine, British Heart Foundation Centre for Research Excellence, Radcliffe Department of Medicine, John Radcliffe Hospital, United Kingdom (E.M., D.J., J.P., P.C., K.M.C.); Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom (E.M., J.P., P.C., K.M.C.); and Sir William Dunn School of Pathology, University of Oxford, United Kingdom (A.J.I., L.T., D.R.G.).
authors.forename: Keith M
authors.initials: KM
authors.lastname: Channon
mesh_terms: D019264:Adoptive Transfer; D000804:Angiotensin II; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001014:Aortic Aneurysm / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D058948:Cell Tracking / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D037502:Galectin 3 / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D017452:Receptors, IgG / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D000097382:CD68 Molecule
chemical_list: D000804:Angiotensin II; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D001057:Apolipoproteins E; D039481:CD11b Antigen; D039521:CD11c Antigen; D037502:Galectin 3; D049452:Green Fluorescent Proteins; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C485095:Lgals3 protein, mouse; C036763:monocyte-macrophage differentiation antigen
keywords: GFP; atherosclerosis; macrophage; model; monocyte; mouse; trafficking