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Glomerular monocyte-macrophage features in ANCA-positive renal vasculitis and cryoglobulinemic nephritis
Maria Pia Rastaldi1, Franco Ferrario1, Andor Crippa1
1Renal Immunopathology Center, San Carlo Borromeo Hospital, Milan, Italy.
Abstract:
Although it is widely known that many macrophages are present in glomeruli of antineutrophil cytoplasmic antibody (ANCA)-positive renal vasculitis (ANCA + RV) and are believed to contribute to necrotizing extracapillary damage, their precise role is not yet completely understood, especially in humans. The goal of this study was to provide evidence of glomerular macrophage properties in human vasculitis. Twenty-five renal biopsies of ANCA + RV and 18 cases of cryoglobulinemic glomerulonephritis (cryoGN), a disease characterized by massive glomerular macrophage infiltration but absence of necrotizing extracapillary lesions, were selected, and macrophage number, adhesion, acute activation, proliferation, and apoptosis were analyzed by immunohistochemistry and in situ hybridization. Accumulation of macrophages in ANCA + RV was found in areas of glomerular active lesions, whereas in cryoGN, they homogeneously occupied the entire glomerular tuft. Considering the areas of accumulation, comparable macrophage numbers were detected in both diseases. Glomerular vascular cell adhesion molecule-1 was found only in ANCA + RV and only in areas of active lesions. Acute macrophage activation (HLA class II, 27E10) and proinflammatory cytokine production (tumor necrosis factor-alpha, interleukin-1alpha) were prominent in ANCA + RV, whereas in cryoGN, 30% of glomerular macrophages seemed activated and cytokine expression was limited to a few glomerular cells (P: = 0.01). Moreover, only in ANCA + RV proliferative markers were shown on glomerular macrophages and apoptotic macrophages were found. From the data, it seems that ANCA + RV and cryoGN differ profoundly in macrophage properties, namely adhesion, proliferation, and apoptotic clearance. Moreover, acute activation and cytokine production seem to be present in a greater number of macrophages in ANCA + RV, giving this disease a stronger severity that could be taken into account for therapeutic strategies.
Insights
Glomerular macrophages exhibit distinct properties in antineutrophil cytoplasmic antibody-associated vasculitis (ANCA+RV) compared to cryoglobulinemic glomerulonephritis (cryoGN). ANCA+RV shows greater macrophage activation, proliferation, and adhesion, indicating increased disease severity.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Macrophages are abundant in ANCA-associated vasculitis (ANCA+RV) glomeruli, implicated in damage, but their specific roles in human disease remain unclear.
- Cryoglobulinemic glomerulonephritis (cryoGN) presents with significant glomerular macrophage infiltration but lacks necrotizing extracapillary lesions, offering a comparative model.
Purpose of the Study:
- To investigate and differentiate glomerular macrophage properties in human ANCA-associated vasculitis (ANCA+RV) versus cryoglobulinemic glomerulonephritis (cryoGN).
- To elucidate the functional characteristics of macrophages in ANCA+RV and their contribution to renal pathology.
Main Methods:
- Analysis of 25 ANCA+RV and 18 cryoGN renal biopsies using immunohistochemistry and in situ hybridization.
- Assessment of macrophage number, adhesion molecule expression (VCAM-1), activation markers (HLA class II, 27E10), cytokine production (TNF-α, IL-1α), proliferation, and apoptosis.
Main Results:
- Macrophages accumulated in active glomerular lesions in ANCA+RV, while homogeneously distributed in cryoGN, with comparable numbers in both.
- Glomerular VCAM-1 was present only in ANCA+RV active lesions.
- Acute macrophage activation, pro-inflammatory cytokine production, proliferation, and apoptosis were significantly more pronounced in ANCA+RV compared to cryoGN.
Conclusions:
- Glomerular macrophage properties, including adhesion, proliferation, and clearance, significantly differ between ANCA+RV and cryoGN.
- ANCA+RV demonstrates a more severe inflammatory profile with greater macrophage activation and cytokine production, suggesting distinct therapeutic implications.