Home LiteratureArticle Details
PMID: 8099859 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

An acute model for IgA-mediated glomerular inflammation in rats induced by monoclonal polymeric rat IgA antibodies.

Clinical and experimental immunology ·Vol. 92 ·No. 3 ·1993-06-00 ·Pages 514-21

Stad RK, Bruijn JA, van Gijlswijk-Janssen DJ, van Es LA, Daha MR

Abstract

An acute model for IgA-mediated glomerular inflammation in rats was induced by the in situ deposition of IgA directly into the glomerular mesangium. F(ab')2 anti-Thy1 MoAb was used to anchor an antigen, DNP (2,4-dinitrophenol), in the glomeruli of rats. Subsequent infusion of rat polymeric (p-) or monomeric (m-) IgA MoAb with specificity for DNP resulted in mesangial deposition of IgA in both groups of rats. However, acute proteinuria was observed only in p-IgA-treated rats and not in PBS- or m-IgA-treated rats. Immunofluorescence analysis revealed deposition of C3 in an identical pattern to that of IgA in the glomeruli of p-IgA-treated rats. No mesangial deposits of C4 or C1q were seen in these animals. Rats receiving m-IgA or PBS displayed no detectable C3, C4 or C1q deposition. The amount of proteinuria in p-IgA-treated rats was related to the amount of deposited C3. The presence of intraglomerular monocytes was only observed 2 days after p-IgA injection. By light microscopy, aneurysm formation, mesangial hypercellularity and matrix expansion were seen only in p-IgA-treated rats. However, by 37 days post-injection complete resolution of the lesions was observed. No histological renal changes were observed in PBS- or m-IgA-treated rats. In conclusion, an acute form of IgA-mediated nephritis in rats was induced by p-IgA but not by m-IgA. This reproducible model provides a basis for further study into the mechanisms of IgA-mediated glomerular inflammation.

MeSH Terms
2,4-Dinitrophenol Acute Disease Animals Antibodies, Monoclonal Antigens, Surface/immunology Complement Hemolytic Activity Assay Complement System Proteins/immunology Dinitrophenols/immunology Disease Models, Animal Fluorescent Antibody Technique Glomerular Mesangium/immunology Glomerulonephritis, IGA/immunology,pathology Hematuria/pathology Immunoglobulin A Male Membrane Glycoproteins/immunology Polymers Proteinuria/pathology Rats Rats, Wistar Thy-1 Antigens
Chemicals
Antibodies, Monoclonal Antigens, Surface Dinitrophenols Immunoglobulin A Membrane Glycoproteins Polymers Thy-1 Antigens Complement System Proteins 2,4-Dinitrophenol
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Stad R K
Department of Nephrology, University Hospital Leiden, The Netherlands.
Bruijn J A
van Gijlswijk-Janssen D J
van Es L A
Daha M R
References (42)
42 references, click to expand
  1. [Intercapillary deposits of IgA-IgG].
    J Urol Nephrol (Paris). 1968 Sep;74(9):694-5 PMID: 4180586
  2. PREPARATION OF PURIFIED ANTI-2,4-DINITROPHENYL ANTIBODIES.
    Methods Med Res. 1964;10:94-102 PMID: 14284950
  3. DNP-antigens activate the alternate pathway of the complement system.
    J Immunol. 1974 Aug;113(2):501-6 PMID: 4858625
  4. Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: differentiation antigens of rat lymphocytes.
    Cell. 1977 Nov;12(3):663-73 PMID: 303545
  5. Delayed removal of renal-bound antigen in decomplemented rabbits with acute serum sickness.
    Clin Exp Immunol. 1978 May;32(2):199-206 PMID: 352585
  6. Deposition of IgA in renal glomeruli of mink affected with Aleutian disease.
    Am J Pathol. 1979 Jul;96(1):227-36 PMID: 111554
  7. Experimental IgA nephropathy.
    J Exp Med. 1979 Nov 1;150(5):1161-73 PMID: 159331
  8. Quantitative studies of in situ immune complex glomerulonephritis in the rat induced by planted, cationized antigen.
    J Exp Med. 1982 Feb 1;155(2):460-74 PMID: 6460074
  9. IgA nephropathy: characterization of the polymeric nature of mesangial deposits by in vitro binding of free secretory component.
    Clin Exp Immunol. 1982 Mar;47(3):527-34 PMID: 7044624
  10. Role of antigen size and charge in immune complex glomerulonephritis.
    Lab Invest. 1982 Aug;47(2):198-205 PMID: 6180247
  11. Experimental IgA nephropathy induced by oral immunization.
    J Exp Med. 1983 Feb 1;157(2):572-82 PMID: 6681626
  12. Preparation of F(ab')2 fragments from mouse IgG of various subclasses.
    J Immunol Methods. 1983 Jan 28;56(2):235-43 PMID: 6402547
  13. Experimental IgA nephropathy in bile duct ligated rats.
    Clin Immunol Immunopathol. 1983 Jun;27(3):369-77 PMID: 6872355
  14. Nondissociating cationic immune complexes can deposit in glomerular basement membrane.
    J Exp Med. 1983 Nov 1;158(5):1561-72 PMID: 6195286
  15. IGA mesangial glomerulonephritis; significance and pathogenesis of segmental-focal glomerular lesions.
    Virchows Arch A Pathol Anat Histopathol. 1983;402(1):11-24 PMID: 6419453
  16. Circulating and mesangial secretory component-binding IgA-1 in primary IgA nephropathy.
    Kidney Int. 1984 Nov;26(5):760-6 PMID: 6441067
  17. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3.
    Immunology. 1985 Mar;54(3):589-99 PMID: 3882559
  18. Spontaneous glomerular IgA deposition in ddY mice: an animal model of IgA nephritis.
    Kidney Int. 1985 May;27(5):756-61 PMID: 4021309
  19. Rat monoclonal antibodies. VI. Production of IgA secreting hybridomas with specificity for the 2,4-dinitrophenyl (DNP) hapten.
    J Immunol Methods. 1986 May 1;89(1):81-7 PMID: 3701070
  20. Mediation of IgA induced lung injury in the rat. Role of macrophages and reactive oxygen products.
    Lab Invest. 1986 May;54(5):499-506 PMID: 3009967
  21. Acute glomerulonephritis after intravenous injection of monoclonal anti-thymocyte antibodies in the rat.
    Immunol Lett. 1986 Mar;12(2-3):109-13 PMID: 3522413
  22. Activation of the alternative pathway of complement by human serum IgA.
    Eur J Immunol. 1987 Mar;17(3):321-6 PMID: 3569402
  23. Complement membrane attack (MAC) in idiopathic IgA-glomerulonephritis.
    Kidney Int. 1987 Mar;31(3):820-9 PMID: 3573542
  24. Intravascular and mucosal immunoglobulin A: two separate but related systems of immune defense?
    Ann Intern Med. 1987 Jun;106(6):892-9 PMID: 3579073
  25. Complement activation in IgA nephropathy.
    Kidney Int. 1987 Apr;31(4):1019-23 PMID: 3586493
  26. Intraglomerular T cells and monocytes in nephritis: study with monoclonal antibodies.
    Kidney Int. 1987 May;31(5):1160-6 PMID: 3496476
  27. Composition of mesangial deposits in IgA nephropathy: complement factors.
    Nephron. 1987;46(2):219 PMID: 3600937
  28. The role of mesangial complement in the hematuria of experimental IgA nephropathy.
    Lab Invest. 1987 Sep;57(3):269-76 PMID: 3306149
  29. Complement activation in experimental IgA nephropathy: an antigen-mediated process.
    Kidney Int. 1987 Dec;32(6):838-44 PMID: 3430967
  30. The commonest glomerulonephritis in the world: IgA nephropathy.
    Q J Med. 1987 Sep;64(245):709-27 PMID: 3329736
  31. Binding, internalization and degradation of soluble aggregates of human secretory IgA by resident rat peritoneal macrophages.
    Immunology. 1988 Aug;64(4):703-8 PMID: 3169844
  32. Chronic serum sickness glomerulonephritis: removal of glomerular antigen and electron-dense deposits is largely dependent on plasma complement.
    Clin Exp Immunol. 1988 Oct;74(1):126-30 PMID: 3219798
  33. Activation of rat complement by soluble and insoluble rat IgA immune complexes.
    Eur J Immunol. 1988 Dec;18(12):1873-80 PMID: 3220102
  34. IgA nephropathy: pathogenesis of the most common form of glomerulonephritis.
    Lab Invest. 1989 Feb;60(2):168-83 PMID: 2644483
  35. Monocyte infiltration and cross-linked fibrin deposition in IgA nephritis and Henoch-Schoenlein purpura nephritis.
    Clin Nephrol. 1989 Sep;32(3):107-12 PMID: 2791360
  36. Physiology of the mesangial cell.
    Physiol Rev. 1989 Oct;69(4):1347-424 PMID: 2678170
  37. The effect of antibody isotype and antigenic epitope density on the complement-fixing activity of immune complexes: a systematic study using chimaeric anti-NIP antibodies with human Fc regions.
    Clin Exp Immunol. 1991 Apr;84(1):1-8 PMID: 1707767
  38. Deposition of IgA is associated with macrophage influx in the kidney of rats.
    Scand J Immunol. 1991 Jul;34(1):81-9 PMID: 2068534
  39. In vivo activation of complement by IgA in a rat model.
    Clin Exp Immunol. 1992 Jan;87(1):138-43 PMID: 1733628
  40. Pathogenesis of IgA nephropathy.
    Kidney Int. 1992 Jun;41(6):1720-9 PMID: 1501427
  41. IgA nephropathy in patients with congenital C9 deficiency.
    Kidney Int. 1992 Nov;42(5):1253-8 PMID: 1453611
  42. IgA-deposits in cutaneous blood-vessel walls and mesangium in Henoch-Schönlein syndrome.
    Lancet. 1973 Apr 21;1(7808):892-3 PMID: 4123449
Article Info
Journal
Clinical and experimental immunology
Abbr.
Clin Exp Immunol
ISSN
0009-9104
Published
1993-06-00
Pages
514-21
Language
English
Region
England
NLM ID
0057202
PMCID
PMC1554775
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]