Decreased tumour necrosis factor-α production by monocytes of granulomatosis with polyangiitis

• Published in: Scandinavian journal of rheumatology 2014-10, Vol.43 (5), p.403-408
• Main Authors: Park, JK, Lee, EB, Song, YW
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Biopsy; Case-Control Studies; Cells, Cultured; Female; Granuloma, Respiratory Tract - metabolism; Granuloma, Respiratory Tract - pathology; Humans; Lipopolysaccharides - pharmacology; Lung - metabolism; Lung - pathology; Macrophage Activation; Male; Microscopic Polyangiitis - metabolism; Microscopic Polyangiitis - pathology; Middle Aged; Monocytes - drug effects; Monocytes - metabolism; Monocytes - pathology; Receptors, Cell Surface - metabolism; Receptors, IgG - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - metabolism; Vasculitis, Central Nervous System - metabolism; Vasculitis, Central Nervous System - pathology
• ISSN: 0300-9742; 1502-7732
• DOI: 10.3109/03009742.2014.894568

Objectives: 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. Method: 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.