title: Glomerular monocyte-macrophage features in ANCA-positive renal vasculitis and cryoglobulinemic nephritis.
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.
authors.affiliation: Renal Immunopathology Center, San Carlo Borromeo Hospital, Milan, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rastaldi
authors.affiliation: Renal Immunopathology Center, San Carlo Borromeo Hospital, Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Ferrario
authors.affiliation: Renal Immunopathology Center, San Carlo Borromeo Hospital, Milan, Italy.
authors.forename: Andor
authors.initials: A
authors.lastname: Crippa
authors.affiliation: Department of Pathology, San Raffaele Hospital, Milan, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Dell'antonio
authors.affiliation: Department of Nephrology, San Anna Hospital, Como, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Casartelli
authors.affiliation: Department of Nephrology, San Anna Hospital, Como, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Grillo
authors.affiliation: Renal Immunopathology Center, San Carlo Borromeo Hospital, Milan, Italy.|Division of Nephrology, San Carlo Borromeo Hospital, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Amico
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D017209:Apoptosis; D002448:Cell Adhesion; D002455:Cell Division; D003449:Cryoglobulinemia / Q000150:complications; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D009393:Nephritis / Q000473:pathology; D012016:Reference Values; D012079:Renal Circulation; D014657:Vasculitis / Q000276:immunology* / Q000473:pathology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic