title: Decreased tumour necrosis factor-α production by monocytes of granulomatosis with polyangiitis.
abstract: OBJECTIVE
  We hypothesized that monocytes in patients with granulomatosis with polyangiitis (GPA) are polarized towards alternative activation with decreased tumour necrosis factor (TNF)-α production and that tissue-infiltrating monocytes/macrophages in granulomatous GPA lesions express CD163, a marker of alternative macrophage activation.
  
  
  METHODS
  CD16+ monocytes in peripheral blood mononuclear cells (PBMCs) were quantified by flow cytometry. Monocytes were stimulated with increasing concentrations of lipopolysaccharide (LPS), and TNF-α production was measured at 4 and 24 h. CD163 expression in lung biopsies of patients with GPA was detected by immunohistochemistry.
  
  
  RESULTS
  Circulating CD16+ monocytes were more frequent in GPA patients compared to controls (4.7 ± 2.8% vs. 1.9 ± 1.2%, p < 0.001). Upon activation with LPS, TNF-α production did not differ between CD16+ and CD16- monocytes. Stimulated monocytes from GPA patients produced significantly less TNF-α compared with monocytes from healthy controls (2903 ± 1320 pg/mL vs. 8335 ± 4569 pg/mL, p < 0.001). Macrophages expressing CD163 were enriched in granulomatous lung lesions of GPA patients.
  
  
  CONCLUSIONS
  Decreased TNF-α production by circulating monocytes and CD163 overexpression by tissue monocytes/macrophages in granulomatous pulmonary lesions may suggest that monocytes/macrophages are alternatively activated in GPA.
authors.affiliation: Division of Rheumatology, Department of Medicine, Seoul National University Hospital , Seoul , Korea.
authors.forename: Jk
authors.initials: J
authors.lastname: Park
authors.forename: E B
authors.initials: EB
authors.lastname: Lee
authors.forename: Y W
authors.initials: YW
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D015769:Granuloma, Respiratory Tract / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation; D008297:Male; D055953:Microscopic Polyangiitis / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism; D020293:Vasculitis, Central Nervous System / Q000378:metabolism* / Q000473:pathology; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha