Alfonso Rubio-Navarro1, Juan Manuel Amaro Villalobos1, Jes S Lindholt2, Irene Buendía1, Jesús Egido3, Luis Miguel Blanco-Colio1, Rafael Samaniego4, Olivier Meilhac5, Jean Baptiste Michel6, José Luis Martín-Ventura1, Juan Antonio Moreno7. 1. Vascular, Renal and Diabetes Research Lab., IIS-Fundación Jiménez Díaz, Autónoma University, Madrid, Spain. 2. Elitary Research Centre of Individualized Medicine in Arterial Disease (CIMA), Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Denmark. 3. 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. 4. Confocal Microscopy Unit, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. 5. INSERM U1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Université de La Réunion, CHU de La Réunion, Saint-Denis, France. 6. INSERM UMRS 1148 Laboratory for Vascular Translational Science, Bichat Hospital, Paris, France. 7. Vascular, Renal and Diabetes Research Lab., IIS-Fundación Jiménez Díaz, Autónoma University, Madrid, Spain. Electronic address: jamoreno@fjd.es.
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. METHODS AND RESULTS:CD163 mRNAand 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.
RCT Entities:
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. METHODS AND 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: James Kim; Jenifer Gómez-Pastora; Mitchell Weigand; Marnie Potgieter; Nicole A Walters; Eduardo Reátegui; Andre F Palmer; Mark Yazer; Maciej Zborowski; Jeffrey J Chalmers Journal: Cytometry A Date: 2019-04-08 Impact factor: 4.355