1988 Fiscal Year Final Research Report Summary
Etiology and mechanisms of glomerular injuries in IgA nephropathy
| Project/Area Number |
62570150
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | Okinaka Memorial Institute for Medical Research |
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Principal Investigator |
ENDO Yuzo Okinaka Memorial Institute for Medical Research, Chief Research Fellow, 主任研究員 (00124305)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Mitsuru Toranomon Hospital, Department of Pathology, Director, 細菌検査部, 部長 (60010047)
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| Project Period (FY) |
1987 – 1988
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| Keywords | IgA immune complexes / Glomerular injury / Gram negative bacteria / Mouse model of IgA nephropathy / 粘膜免疫系 |
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| Research Abstract |
1. Polymeric IgA was detected in the glomerular eluates which were obtained from cryostat sections ( 500 to 800 pieces ) of renal tissue of the autopsy cases positive for glomerular IgA and C3 deposition with liver cirrhosis, idiopathic interstitial pneumonia or diffuse panbronchiolitis. One of the antigenic substances reacting with these IgA antibodies deposited in the glomeruli indicated to be Escherlichia coli ( E. coli ), Pseudomonas aeruginosa as well as lipopolysaccharide ( LPS ).
We intended to do the experiment and tried to establish a mouse model of IgA nephropathy by using the Gram negative bacteria such as three strains of Pseudo-monas aeruginosa ( 0 antigen 1, 2, 3 ) kindly gifted from Dr.Honma of Kitasato University, E. coli, Hemophilus influenzae ( H. inf ), Klebsiella pneumoniae purchased from Riken and two kinds of LPS. C3H/HeN female mice were composed of two groups such as one group ( po ) of oral intake ad libitum of tap water con-taining of each bacterial species as
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well as LPS and another group ( ip ) of weekly intraperitoneal administration of each bacterial species with complete Freund adjuvant. Mice were the age of 5 weeks at the start of this experiment and sacrificed at 10, 20 and weeks. Sera and organs were obtained at each sacrifice. Histological, immunohistological and ultrastructural findings of the kidneys were analysed. In the ip group, immunofluorescence positivity of glomerular IgA and C3 was increased, compared with that of the po group. Histological features of the ip group showed mesangial thickening and those of the mice ( H.inf ) were closely similar to those of human IgA nephropathy.
3. Perspectives of this project: (1) analysis of those bacterial cell wall (2) correlation of bacterial components and mouse or human IgA deposited in the glomeruli (3) interaction of complement components and active oxygen radicals in glomerular injuries of mouse IgA nephropathy. (4) dynamics of IgA mediated immune mechanisms in mucosal stimulation by bacteria. Less
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