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| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
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| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
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*
Renal Immunopathology Center, San Carlo Borromeo Hospital, Milan,
Italy.
§
Division of Nephrology, San Carlo Borromeo Hospital, Milan,
Italy.
Department of Pathology, San Raffaele Hospital, Milan, Italy.
Department of Nephrology, San Anna Hospital, Como, Italy.
Correspondence to Dr. Maria Pia Rastaldi, Renal Immunopathology Center, Division of Nephrology, San Carlo Borromeo Hospital, Via Pio II, 3, 20153 Milan, Italy. Phone: 39240222343; Fax: 39240222222; E-mail: mp.rastaldi{at}oscb.sined.net
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-
, interleukin-1) 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.
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