1999 Fiscal Year Final Research Report Summary
The role of the autoantibody in lupus rephritis
Project/Area Number |
10671006
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | Juntendo University |
Principal Investigator |
FUNABIKI Kazuhiko Juntendo University, School of Medicine, Assistant Professor, 医学部, 講師 (70219088)
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Project Period (FY) |
1998 – 1999
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Keywords | Fc recepter / glomerulonephritis / FcRγchain deficient mice / NZB / NZWF1 mice / anti-GBM antibody / bone marrow transplantation |
Research Abstract |
It has been clarified that Fc receptor (FcR) plays a critical role in glomerulonephritis (GN). Using FcRγ chain (γ(-/-)) and FcγR IIB deficient mice, we have already proved that prognosis of experimental GN was dependent on the phenotype of FcR. To investigate whether the quantity of FcR expression may have an effect on the severity of GN, we generated several chimeric mice from γ(-/-) mice for two different models, namely 1) New Zealand Black (NZB)/New Zealand White (NZW) F1 mice (B/WF 1 mice) as a chronic and spontaneous model and 2) anti-GBM antibody induced GN (anti-GBM GN) as an acute and passive model. In the first experiment, γ(-/-) mice were backcrossed to NZB and NZW mice for more than seven generations. Γ(+/-) NZB males and γ(+/-)NZW females were bred to generate 3 kinds of B/WF 1 mice; γ(-/-)B/WF 1, γ(+/-)B/WF 1 and γ(+/+)B/WF 1 mice. Although GN in γ(+/+)B/WF 1 mice was obviously induced as same in B/WF 1 mice, renal injuries were completely abolished in γ(-/-)B/WF 1 mice. Interestingly, onset of GN in γ(+/-)B/WF 1 mice was obviously delayed and they significantly survived longer as compared to γ(+/+)B/WF 1 mice. In the second experiment, we induced anti-GBM GN in γW chimeric mice which were wild type mice (WT) transplanted with bone marrows from γ(-/-) mice. No renal injuries were found even at day 150 after the injection of nephrotoxic serum in γW mice irradiated at 1200 rad before the transplantation. While, in γW mice irradiated at 800 rad, lupus like GN was gradually revealed after day 70, concomitant with a recovery of WT bone marrows and WT peripheral blood leukocytes with functional FcRs. Our data indicated that quantitative threshold of FcR expression may underlie in the pathogenesis of GN.
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