title: Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in abdominal aortic aneurysm.
abstract: BACKGROUND
  Increased hemoglobin (Hb) accumulation was reported in abdominal aortic aneurysms (AAAs). CD163 is a macrophage receptor involved in tissue Hb clearance, however its role in AAA has not been reported. We investigated the role of Hb on monocyte recruitment and differentiation towards CD163 expressing macrophages ex vivo, in vitro and in human AAA.
  
  
  RESULTS
  CD163 mRNA and protein expression was significantly higher in human AAA (n=7) vs. healthy wall (n=6). CD163 was predominantly found in adventitia of AAA, coinciding with areas rich in hemosiderin and adjacent to neoangiogenic microvessels. Dual CD14/CD163 expression was observed in recently infiltrated monocytes surrounding microvessels. A higher release of soluble CD163 was observed in the conditioned medium from AAA (AAA-CM, n=10), mainly in the adventitial layer. Similar to Hb, AAA-CM induced CD163-dependent monocyte chemotaxis, especially on circulating monocytes from AAA patients. Hb or AAA-CM promoted differentiation towards CD163(high)/HLA-DR(low)-expressing macrophages, with enhanced Hb uptake, increased anti-inflammatory IL-10 secretion and decreased pro-inflammatory IL-12p40 release. All these effects were partially suppressed when Hb was removed from AAA-CM. Separate analysis on circulating monocytes reported increased percentage of pre-infiltrating CD14(++)CD16(+) monocytes in patients with AAA (n=21), as compared to controls (n=14). A significant increase in CD163 expression in CD14(++)CD16(+) monocyte subpopulation was observed in AAA patients.
  
  
  CONCLUSIONS
  The presence of Hb in the adventitial AAA-wall promotes the migration and differentiation of activated circulating monocytes in AAA patients, explaining the existence of a protective CD163-macrophage phenotype that could take up the Hb present in the AAA-wall, avoiding its injurious effects.
authors: Vascular, Renal and Diabetes Research Lab., IIS-Fundación Jiménez Díaz, Autónoma University, Madrid, Spain.
authors: Alfonso
authors: A
authors: Rubio-Navarro
authors: Vascular, Renal and Diabetes Research Lab., IIS-Fundación Jiménez Díaz, Autónoma University, Madrid, Spain.
authors: Juan Manuel
authors: JM
authors: Amaro Villalobos
authors: Elitary Research Centre of Individualized Medicine in Arterial Disease (CIMA), Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Denmark.
authors: Jes S
authors: JS
authors: Lindholt
authors: Vascular, Renal and Diabetes Research Lab., IIS-Fundación Jiménez Díaz, Autónoma University, Madrid, Spain.
authors: Irene
authors: I
authors: Buendía
authors: Vascular, Renal and Diabetes Research Lab., IIS-Fundación Jiménez Díaz, Autónoma University, Madrid, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Spain.
authors: Jesús
authors: J
authors: Egido
authors: Vascular, Renal and Diabetes Research Lab., IIS-Fundación Jiménez Díaz, Autónoma University, Madrid, Spain.
authors: Luis Miguel
authors: LM
authors: Blanco-Colio
authors: Confocal Microscopy Unit, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors: Rafael
authors: R
authors: Samaniego
authors: INSERM U1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Université de La Réunion, CHU de La Réunion, Saint-Denis, France.
authors: Olivier
authors: O
authors: Meilhac
authors: INSERM UMRS 1148 Laboratory for Vascular Translational Science, Bichat Hospital, Paris, France.
authors: Jean Baptiste
authors: JB
authors: Michel
authors: Vascular, Renal and Diabetes Research Lab., IIS-Fundación Jiménez Díaz, Autónoma University, Madrid, Spain.
authors: José Luis
authors: JL
authors: Martín-Ventura
authors: Vascular, Renal and Diabetes Research Lab., IIS-Fundación Jiménez Díaz, Autónoma University, Madrid, Spain. Electronic address: jamoreno@fjd.es.
authors: Juan Antonio
authors: JA
authors: Moreno
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis* / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis* / Q000097:blood*; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000175:diagnosis*; D016764:Cell Polarity / Q000502:physiology; D006454:Hemoglobins / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000097:blood*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006454:Hemoglobins; D011956:Receptors, Cell Surface
keywords: Aortic abdominal aneurysm; CD163; Hemoglobin; Macrophages