Nephritogenicity of anti-proteoglycan antibodies in experimental murine lupus nephritis

N. Kashihara, Hirofumi Makino, Z. Szekanecz, C. R. Waltenbaugh, Y. S. Kanwar

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

BACKGROUND: Cross-reactivity between anti-DNA antibodies and heparan sulfate (HS)/heparan sulfate-proteoglycan (HS-PG) of glomerular basement membrane has been previously reported. Conceivably, this determines the final outcome of glomerular injury in lupus nephritis. EXPERIMENTAL DESIGN: We investigated the status of glomerular injury in NZB/NZW F1 mice after the administration of rabbit anti-HS-PG antibody (experiment group). The controls received normal rabbit IgG only. RESULTS: All experimental animals became proteinuric 2 weeks after the administration of anti-HS-PG. The animals of the older age group (16 weeks) had significant hematuria as well. Their glomeruli exhibited hypercellularity with a heavy influx of polymorphonuclear leukocytes and monocytes into their capillaries, and some of them exhibited crescentic changes. Electron-dense deposits were present in subepithelial, subendothelial, and mesangial regions of the glomeruli. The control group had normocellular glomeruli with a few mesangial deposits. Mouse IgG and C3 displayed a granular pattern of immunofluorescence in the experimental group. Anti-rabbit IgG titers in the serum were higher in the control group, which lower in the renal glomerular eluates. No significant differences were observed in the concentrations of anti-dsDNA and -ssDNA either in the sera or in the eluates. There was also no difference between the control and experimental group in terms of antibody synthesis by the splenic lymphocytes and their proliferation subsequent to antigenic challenge. CONCLUSIONS: Data suggest that administration of anti-HS-PG accentuates the glomerular injury during the natural course of lupus nephritis in (NZB/NZW F1 mice; seemingly these two antibodies (anti-HS-PG and -DNA) do not competitively inhibit the binding of the other to the same anionic sites of glomerular basement membrane enriched with heparan sulfate in vivo.

Original languageEnglish
Pages (from-to)752-760
Number of pages9
JournalLaboratory Investigation
Volume67
Issue number6
Publication statusPublished - Dec 1 1992
Externally publishedYes

Fingerprint

Lupus Nephritis
Heparitin Sulfate
Proteoglycans
Anti-Idiotypic Antibodies
Glomerular Basement Membrane
Rabbits
Control Groups
Wounds and Injuries
Immunoglobulin G
Heparan Sulfate Proteoglycans
Antibodies
Antinuclear Antibodies
Hematuria
Serum
Fluorescent Antibody Technique
Monocytes
Neutrophils
Age Groups
Lymphocytes
Electrons

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Kashihara, N., Makino, H., Szekanecz, Z., Waltenbaugh, C. R., & Kanwar, Y. S. (1992). Nephritogenicity of anti-proteoglycan antibodies in experimental murine lupus nephritis. Laboratory Investigation, 67(6), 752-760.

Nephritogenicity of anti-proteoglycan antibodies in experimental murine lupus nephritis. / Kashihara, N.; Makino, Hirofumi; Szekanecz, Z.; Waltenbaugh, C. R.; Kanwar, Y. S.

In: Laboratory Investigation, Vol. 67, No. 6, 01.12.1992, p. 752-760.

Research output: Contribution to journalArticle

Kashihara, N, Makino, H, Szekanecz, Z, Waltenbaugh, CR & Kanwar, YS 1992, 'Nephritogenicity of anti-proteoglycan antibodies in experimental murine lupus nephritis', Laboratory Investigation, vol. 67, no. 6, pp. 752-760.
Kashihara N, Makino H, Szekanecz Z, Waltenbaugh CR, Kanwar YS. Nephritogenicity of anti-proteoglycan antibodies in experimental murine lupus nephritis. Laboratory Investigation. 1992 Dec 1;67(6):752-760.
Kashihara, N. ; Makino, Hirofumi ; Szekanecz, Z. ; Waltenbaugh, C. R. ; Kanwar, Y. S. / Nephritogenicity of anti-proteoglycan antibodies in experimental murine lupus nephritis. In: Laboratory Investigation. 1992 ; Vol. 67, No. 6. pp. 752-760.
@article{27a27d5ad6a04a4aa0d1129dc4e983ba,
title = "Nephritogenicity of anti-proteoglycan antibodies in experimental murine lupus nephritis",
abstract = "BACKGROUND: Cross-reactivity between anti-DNA antibodies and heparan sulfate (HS)/heparan sulfate-proteoglycan (HS-PG) of glomerular basement membrane has been previously reported. Conceivably, this determines the final outcome of glomerular injury in lupus nephritis. EXPERIMENTAL DESIGN: We investigated the status of glomerular injury in NZB/NZW F1 mice after the administration of rabbit anti-HS-PG antibody (experiment group). The controls received normal rabbit IgG only. RESULTS: All experimental animals became proteinuric 2 weeks after the administration of anti-HS-PG. The animals of the older age group (16 weeks) had significant hematuria as well. Their glomeruli exhibited hypercellularity with a heavy influx of polymorphonuclear leukocytes and monocytes into their capillaries, and some of them exhibited crescentic changes. Electron-dense deposits were present in subepithelial, subendothelial, and mesangial regions of the glomeruli. The control group had normocellular glomeruli with a few mesangial deposits. Mouse IgG and C3 displayed a granular pattern of immunofluorescence in the experimental group. Anti-rabbit IgG titers in the serum were higher in the control group, which lower in the renal glomerular eluates. No significant differences were observed in the concentrations of anti-dsDNA and -ssDNA either in the sera or in the eluates. There was also no difference between the control and experimental group in terms of antibody synthesis by the splenic lymphocytes and their proliferation subsequent to antigenic challenge. CONCLUSIONS: Data suggest that administration of anti-HS-PG accentuates the glomerular injury during the natural course of lupus nephritis in (NZB/NZW F1 mice; seemingly these two antibodies (anti-HS-PG and -DNA) do not competitively inhibit the binding of the other to the same anionic sites of glomerular basement membrane enriched with heparan sulfate in vivo.",
author = "N. Kashihara and Hirofumi Makino and Z. Szekanecz and Waltenbaugh, {C. R.} and Kanwar, {Y. S.}",
year = "1992",
month = "12",
day = "1",
language = "English",
volume = "67",
pages = "752--760",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Nephritogenicity of anti-proteoglycan antibodies in experimental murine lupus nephritis

AU - Kashihara, N.

AU - Makino, Hirofumi

AU - Szekanecz, Z.

AU - Waltenbaugh, C. R.

AU - Kanwar, Y. S.

PY - 1992/12/1

Y1 - 1992/12/1

N2 - BACKGROUND: Cross-reactivity between anti-DNA antibodies and heparan sulfate (HS)/heparan sulfate-proteoglycan (HS-PG) of glomerular basement membrane has been previously reported. Conceivably, this determines the final outcome of glomerular injury in lupus nephritis. EXPERIMENTAL DESIGN: We investigated the status of glomerular injury in NZB/NZW F1 mice after the administration of rabbit anti-HS-PG antibody (experiment group). The controls received normal rabbit IgG only. RESULTS: All experimental animals became proteinuric 2 weeks after the administration of anti-HS-PG. The animals of the older age group (16 weeks) had significant hematuria as well. Their glomeruli exhibited hypercellularity with a heavy influx of polymorphonuclear leukocytes and monocytes into their capillaries, and some of them exhibited crescentic changes. Electron-dense deposits were present in subepithelial, subendothelial, and mesangial regions of the glomeruli. The control group had normocellular glomeruli with a few mesangial deposits. Mouse IgG and C3 displayed a granular pattern of immunofluorescence in the experimental group. Anti-rabbit IgG titers in the serum were higher in the control group, which lower in the renal glomerular eluates. No significant differences were observed in the concentrations of anti-dsDNA and -ssDNA either in the sera or in the eluates. There was also no difference between the control and experimental group in terms of antibody synthesis by the splenic lymphocytes and their proliferation subsequent to antigenic challenge. CONCLUSIONS: Data suggest that administration of anti-HS-PG accentuates the glomerular injury during the natural course of lupus nephritis in (NZB/NZW F1 mice; seemingly these two antibodies (anti-HS-PG and -DNA) do not competitively inhibit the binding of the other to the same anionic sites of glomerular basement membrane enriched with heparan sulfate in vivo.

AB - BACKGROUND: Cross-reactivity between anti-DNA antibodies and heparan sulfate (HS)/heparan sulfate-proteoglycan (HS-PG) of glomerular basement membrane has been previously reported. Conceivably, this determines the final outcome of glomerular injury in lupus nephritis. EXPERIMENTAL DESIGN: We investigated the status of glomerular injury in NZB/NZW F1 mice after the administration of rabbit anti-HS-PG antibody (experiment group). The controls received normal rabbit IgG only. RESULTS: All experimental animals became proteinuric 2 weeks after the administration of anti-HS-PG. The animals of the older age group (16 weeks) had significant hematuria as well. Their glomeruli exhibited hypercellularity with a heavy influx of polymorphonuclear leukocytes and monocytes into their capillaries, and some of them exhibited crescentic changes. Electron-dense deposits were present in subepithelial, subendothelial, and mesangial regions of the glomeruli. The control group had normocellular glomeruli with a few mesangial deposits. Mouse IgG and C3 displayed a granular pattern of immunofluorescence in the experimental group. Anti-rabbit IgG titers in the serum were higher in the control group, which lower in the renal glomerular eluates. No significant differences were observed in the concentrations of anti-dsDNA and -ssDNA either in the sera or in the eluates. There was also no difference between the control and experimental group in terms of antibody synthesis by the splenic lymphocytes and their proliferation subsequent to antigenic challenge. CONCLUSIONS: Data suggest that administration of anti-HS-PG accentuates the glomerular injury during the natural course of lupus nephritis in (NZB/NZW F1 mice; seemingly these two antibodies (anti-HS-PG and -DNA) do not competitively inhibit the binding of the other to the same anionic sites of glomerular basement membrane enriched with heparan sulfate in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0027104121&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027104121&partnerID=8YFLogxK

M3 - Article

VL - 67

SP - 752

EP - 760

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 6

ER -