title: Osteopontin affects macrophage polarization promoting endocytic but not inflammatory properties.
abstract: Macrophages are the main drivers of obesity-induced adipose tissue (AT) inflammation that causes insulin resistance. Macrophages polarize toward different inflammatory (M1) or protective (M2) phenotypes. Osteopontin (OPN) is an inflammatory cytokine highly expressed in AT in obesity and known to be involved in chronic inflammatory processes. It was hypothesized that OPN polarizes macrophages into a proinflammatory phenotype.
  
  
  
  AT macrophages (ATMs) of OPN-deficient (Spp1(-/-) ) and wild-type C57BL/6 (WT) mice with obesity and bone marrow-derived macrophages (BMDMs) of Spp1(-/-) and WT mice as well as human monocyte-derived macrophages (MDMs) polarized in the presence of OPN were investigated.
  
  
  
  While ATM infiltration was lower in Spp1(-/-) upon high-fat diet, Spp1(-/-) ATMs expressed more M1 and less M2 markers but less tumor necrosis factor-α compared with WT. There was no effect of OPN deficiency on BMDM polarization. In human MDMs, the presence of OPN during polarization ambiguously altered M1/M2-related marker expression and diminished LPS-induced inflammatory cytokine production. Strikingly, phagocytic activity was elevated by the presence of OPN during polarization in both human MDMs and murine BMDMs.
  
  
  
  In contradiction to our hypothesis, data indicated that OPN does not induce inflammatory macrophages but was a signal to induce phagocytosis, which may be required due to increased adipocyte death in obesity.
authors.affiliation: Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.|Department of Health, Section Biomedical Science, FH Campus Wien, University of Applied Sciences, Vienna, Austria.
authors.forename: Karina
authors.initials: K
authors.lastname: Schuch
authors.affiliation: Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wanko
authors.affiliation: Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.|Department of Health, Section Biomedical Science, FH Campus Wien, University of Applied Sciences, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ambroz
authors.affiliation: Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.|Department of Health, Section Biomedical Science, FH Campus Wien, University of Applied Sciences, Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Castelo-Rosa
authors.affiliation: Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.
authors.forename: Verónica
authors.initials: V
authors.lastname: Moreno-Viedma
authors.affiliation: Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Grün
authors.affiliation: Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Leitner
authors.affiliation: AFFiRiS AG, Vienna, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Staffler
authors.affiliation: Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.|Department of Pediatrics and Adolescent Medicine, Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Medical University of Vienna, Vienna, Austria.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Zeyda
authors.affiliation: Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
mesh_terms: D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D007249:Inflammation / Q000503:physiopathology; D007333:Insulin Resistance; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000503:physiopathology*; D053495:Osteopontin / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin