| Project/Area Number |
08457068
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Ehime University (1997)
Tohoku University (1996) |
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Principal Investigator |
NOSE Masato Ehime Univ., Sch., Med., Pathol., Prof., 医学部, 教授 (70030913)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | lupus nephritis / nephritogenic antibody / vascular endothelial cell / endocytosis / phagocytosis / E-selectin / soluble E-selectin / transgenic mice |
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| Research Abstract |
Lupus nephritis has been considered to be mainly generated by the type II and/or III allergic reactions mediated by autoantibodies. We previously developed nephritogenic antibody-producing hybridoma clones derived from a diseased mouse of an MRL/lpr strain, which can generate glomerulonephritis (GN) when injected into normal mice. One clone induced a wire-loop type of glomerular lesions, characterized by the deposition of osminophilic material in subendothelial and mesangial regions. These glomerular lesions seemed to be generated by active endocytosis of the antibodies by endothelial cells. Actually, aggressive endocytosis of the antibodies by cultured human umbilical vein endothelial cells (HUVEC) in vitro was observed after a short period of cultivation, which was mediated by transendothelial transport and lysosomal system of the HUVEC,but not via Fc receptors and oxidized LDL receptors. Similar phenomena were found when the serum IgG obtained from particular reno-vascular disease patients were reacted. This finding may be important to propose a novel category in reno-vascular diseases. Another clone induced a proliferative type of glomerular lesions, characterized by the accumulation of neutrophils and macrophages, following E-selectin expression on glomerular endothelial cells. This type of antibodies by themselves had a potency to induce the expression of E-selection on HUVEC in vitro, as also confirmed in a transcription level, via endocytotic process. The development of these lesions was not induced in the trainsgenic mice producing E-selectin in a soluble form. Thus, the initial event inducing E-selectin expression by the antibodies on endothelial cells may play a critical role for the development of GN.The mechanisms of such kinds of cell injury by antibody molecules are novel ones which cannot be explained in term of any known form of allergic reaction.
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