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Decreased tumour necrosis factor-α production by monocytes of granulomatosis with polyangiitis
1Division of Rheumatology, Department of Medicine, Seoul National University Hospital , Seoul , Korea.
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.
Insights
Monocytes in granulomatosis with polyangiitis (GPA) patients show alternative activation, producing less tumor necrosis factor-alpha (TNF-α). Tissue macrophages in GPA lesions express CD163, indicating alternative activation in this disease.
Area of Science:
- Immunology
- Pathology
Background:
- Granulomatosis with polyangiitis (GPA) is an autoimmune disease characterized by inflammation.
- Monocyte and macrophage polarization plays a critical role in inflammatory processes.
Purpose of the Study:
- To investigate if monocytes in GPA patients exhibit alternative activation.
- To determine if tissue macrophages in GPA lesions express CD163, a marker of alternative activation.
Main Methods:
- Quantification of CD16+ monocytes in peripheral blood mononuclear cells (PBMCs) via flow cytometry.
- Measurement of TNF-α production after lipopolysaccharide (LPS) stimulation.
- Immunohistochemical detection of CD163 in lung biopsies from GPA patients.
Main Results:
- GPA patients had a higher frequency of circulating CD16+ monocytes compared to controls.
- Stimulated monocytes from GPA patients produced significantly less TNF-α than those from healthy controls.
- CD163-expressing macrophages were found in granulomatous lung lesions of GPA patients.
Conclusions:
- Decreased TNF-α production by circulating monocytes suggests alternative activation.
- CD163 overexpression in tissue macrophages indicates alternative activation in GPA lesions.
- These findings suggest a role for alternatively activated monocytes/macrophages in the pathogenesis of GPA.
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