Involvement of activated periglomerular leukocytes in the rupture of Bowman's capsule and glomerular crescent progression in experimental glomerulonephritis

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Abstract

BACKGROUND: In an experimental model of crescentic glomerulonephritis, we have investigated whether periglomerular leukocytes are involved in (a), the disruption of Bowman's capsule (BC), and (b) the progression of cellular crescents. EXPERIMENTAL DESIGN: Experimental crescentic glomerulonephritis was induced in inbred Sprague-Dawley rats using passive accelerated anti- glomerular basement membrane disease. Groups of 4 animals were sacrificed at 3, 7, 14, 21, and 28 days after administration of nephrotoxic serum. RESULTS: Periglomerular infiltration of macrophages and T cells was evident at day 3, although focal accumulation of activated mononuclear cells (IL-2R+) was not apparent in this area until day 14. BC rupture in some glomeruli was first evident at day 14, and this was seen in all 12 animals from days 14 to 28. Similarly, glomerular crescent formation was first apparent at day 14, and from days 14 to 28, 11 of 12 animals displayed crescent formation (25 to 74% crescentic glomeruli). Examination of glomeruli (≥200/animal) within periodic acid-Shiff stained sections found that BC disruption invariably occurred at sites of prominent focal periglomerular mononuclear cell infiltration. Monoclonal antibody labeling revealed that T cells and IL-2R+ cells were restricted to focal infiltrates at sites of BC rupture, whereas macrophages were more widely distributed throughout the periglomerular area. A key finding was that while BC disruption occurred in both the presence and the absence of crescent formation, it was always associated with prominent periglomerular leukocytic infiltration. In this model, most cellular crescents contained leukocytes (88.8 ± 2.1%). In the presence of an intact BC, macrophages constituted the predominant leukocyte cell type within these crescents. However, when BC was ruptured, although the number of macrophages remained unchanged, a marked accumulation of both T cells and IL-2R+ cells occurred within crescents. Progressive fibrous organization of cellular crescents was observed only in those glomeruli in which BC was disrupted. CONCLUSIONS: The results suggest that: (a) activated periglomerular mononuclear cells may cause disruption of BC via a delayed-type hypersensitivity mechanism, (b) rupture of BC facilitates entry of activated periglomerular T cells and fibroblasts into Bowman's space leading to progressive fibrous organization of cellular crescents, and (c) disruption of BC may be a general mechanism of progressive glomerular damage mediated by periglomerular leukocytes irrespective of crescent formation.

Original languageEnglish
Pages (from-to)743-751
Number of pages9
JournalLaboratory Investigation
Volume67
Issue number6
Publication statusPublished - 1 Dec 1992
Externally publishedYes

Keywords

  • Interleukin-2 receptor

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