title: Remodeling phenotype of human subcutaneous adipose tissue macrophages.
abstract: BACKGROUND
  Adipose tissue macrophages (ATMs) have become a focus of attention recently because they have been shown to accumulate with an increase in fat mass and to be involved in the genesis of insulin resistance in obese mice. However, the phenotype and functions of human ATMs are still to be defined.
  
  
  RESULTS
  The present study, performed on human subcutaneous AT, showed that ATMs from lean to overweight individuals are composed of distinct macrophage subsets based on the expression of several cell surface markers: CD45, CD14, CD31, CD44, HLA-DR, CD206, and CD16, as assessed by flow cytometry. ATMs isolated by an immunoselection protocol showed a mixed expression of proinflammatory (tumor necrosis factor-alpha, interleukin-6 [IL-6], IL-23, monocyte chemoattractant protein-1, IL-8, cyclooxygenase-2) and antiinflammatory (IL-10, transforming growth factor-beta, alternative macrophage activation-associated cc chemokine-1, cyclooxygenase-1) factors. Fat mass enlargement is associated with accumulation of the CD206+/CD16- macrophage subset that exhibits an M2 remodeling phenotype characterized by decreased expression of proinflammatory IL-8 and cyclooxygenase-2 and increased expression of lymphatic vessel endothelial hyaluronan receptor-1. ATMs specifically produced and released matrix metalloproteinase-9 compared with adipocytes and capillary endothelial cells, and secretion of matrix metalloproteinase-9 from human AT in vivo, assessed by arteriovenous difference measurement, was correlated with body mass index. Finally, ATMs exerted a marked proangiogenic effect on AT-derived endothelial and progenitor cells.
  
  
  CONCLUSIONS
  The present results showed that the ATMs that accumulate with fat mass development exhibit a particular M2 remodeling phenotype. ATMs may be active players in the process of AT development through the extension of the capillary network and in the genesis of obesity-associated cardiovascular pathologies.
authors.affiliation: Equipe AVENIR/INSERM U858, 1 Avenue Jean Poulhès, BP 84225, 31432 Toulouse cedex 4, France. virginie.bourlier@toulouse.inserm.fr
authors.forename: V
authors.initials: V
authors.lastname: Bourlier
authors.forename: A
authors.initials: A
authors.lastname: Zakaroff-Girard
authors.forename: A
authors.initials: A
authors.lastname: Miranville
authors.forename: S
authors.initials: S
authors.lastname: De Barros
authors.forename: M
authors.initials: M
authors.lastname: Maumus
authors.forename: C
authors.initials: C
authors.lastname: Sengenes
authors.forename: J
authors.initials: J
authors.lastname: Galitzky
authors.forename: M
authors.initials: M
authors.lastname: Lafontan
authors.forename: F
authors.initials: F
authors.lastname: Karpe
authors.forename: K N
authors.initials: KN
authors.lastname: Frayn
authors.forename: A
authors.initials: A
authors.lastname: Bouloumié
mesh_terms: D015703:Antigens, CD; D015992:Body Mass Index; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000201:enzymology / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D010641:Phenotype; D050151:Subcutaneous Fat / Q000166:cytology*
chemical_list: D015703:Antigens, CD; D020780:Matrix Metalloproteinase 9