Glomerular monocyte-macrophage features in ANCA-positive renal vasculitis and cryoglobulinemic nephritis

Although it is widely known that many macrophages are present in glomeruli of antineutrophil cytoplasmic antibody (ANCA)-positive renal vasculitis (AN CA+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 pr operties in human vasculitis. Twenty-five renal biopsies of ANCA+RV and 18 cases of cryoglobulinemic glomerulonephritis (cryoGN), a disease characteri zed by massive glomerular macrophage infiltration but absence of necrotizin g extracapillary lesions, were selected, and macrophage number, adhesion, a cute activation, proliferation, and apoptosis were analyzed by immunohistoc hemistry and in situ hybridization. Accumulation of macrophages in ANCA+RV was found in areas of glomerular active lesions, whereas in cryoGN, they ho mogeneously occupied the entire glomerular tuft. Considering the areas of a ccumulation, com-parable 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-alp ha, interleukin-1 alpha) were prominent in ANCA+RV, whereas in cryoGN, 30% of glomerular macrophages seemed activated and cytokine expression was limi ted to a few glomerular cells (P = 0.01). Moreover, only in ANCA+RV prolife rative markers were shown on glomerular macrophages and apoptotic macrophag es were found. From the data, it seems that ANCA+RV and cryoGN differ profo undly in macrophage properties, namely adhesion, proliferation, and apoptot ic 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 strat egies.