title: Role of proinflammatory CD68(+) mannose receptor(-) macrophages in peroxiredoxin-1 expression and in abdominal aortic aneurysms in humans.
abstract: OBJECTIVE
  Abdominal aortic aneurysms (AAAs), dilations of the infrarenal aorta, are characterized by inflammation and oxidative stress. We previously showed increased levels of peroxiredoxin-1 (PRDX-1) in macrophages cultured from AAA patients. The purpose of the study was to determine which subpopulation of macrophages is present in AAAs and is involved in upregulation of PRDX-1 in aneurysmal disease.
  
  
  RESULTS
  This study used immunohistochemistry with antibodies against CD68 and mannose receptor (MR) to determine the subtype of macrophages in AAA tissue samples (n=33); laser capture microdissection to isolate each subtype; and quantitative-reverse transcriptase-polymerase chain reaction, Western blot, and ELISA to assess PRDX-1 mRNA and PRDX-1protein levels in both types. Proinflammatory CD68(+)MR(-) macrophages predominated in adventitial tissue, whereas the intraluminal thrombus contained CD68(+)MR(+) macrophages. The presence of lipids and iron-containing deposits confirmed their phagocytic phenotype. Laser capture microdissection-isolated CD68(+)MR(-) and CD68(+)MR(+) macrophages, characterized by quantitative-reverse transcriptase-polymerase chain reaction (TNF, IL1B, MRC1, and CCL18) and Western blot (stabilin and hemoglobin), validated the microdissected subtypes. PRDX-1 expression was colocalized with CD68(+)MR(-) macrophages. PRDX-1 mRNA and PRDX-1 protein were both more abundant in CD68(+)MR(-) than CD68(+)MR(+) macrophages in AAA.
  
  
  CONCLUSIONS
  These findings suggest that the proteins or mRNAs expressed by the proinflammatory CD68(+)MR(-) macrophages may contribute to aneurysmal pathology.
authors.affiliation: INSERM U744-IPL, 1 rue du professeur Calmette, 59019 Lille cedex, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Boytard
authors.forename: Rafaelle
authors.initials: R
authors.lastname: Spear
authors.forename: Giulia
authors.initials: G
authors.lastname: Chinetti-Gbaguidi
authors.forename: Adelina E
authors.initials: AE
authors.lastname: Acosta-Martin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Vanhoutte
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lamblin
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: Stephan
authors.initials: S
authors.lastname: Haulon
authors.forename: Florence
authors.initials: F
authors.lastname: Pinet
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis*; D001012:Aorta, Abdominal / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis*; D061346:Laser Capture Microdissection; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D018836:Inflammation Mediators; D020780:Matrix Metalloproteinase 9; D054464:Peroxiredoxins; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C515940:PRDX1 protein, human