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Nephritogenicity and α-chain composition of NC1 fractions of type IV collagen from bovine renal basement membrane

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Abstract

Nephritogenicity (anti-GBM-nephritis-inducing activity) and α-chain composition of globular-domain (NC1) fractions of type IV collagen from bovine renal, pulmonary, and placental basement membranes (BMs) was examined by injecting these fractions with adjuvant into WKY/NCrj rats and by Western blotting using epitope-defined monoclonal antibodies to the six different α chains of type IV collagen. A purified nephritogenic fraction from renal BM contained α1–α6(IV)NC1, whereas a non-nephritogenic fraction contained only α1–α2(IV)NC1. Renal and pulmonary NC1 had strong nephritogenic activity; placental NC1 had weak activity. The renal and pulmonary fractions contained α1–α6(IV)NC1, and the placental fraction had a large amount of α1–α2(IV)NC1 and a very small amount of α3–α6(IV)NC1. Immunohistochemical study of bovine renal BM with the monoclonal antibodies revealed that bovine glomerular BM contained α1–α5(IV) chains, but not the α6(IV) chain. The absence of α6(IV) chain in glomerular BM in bovine and in humans indicates that α6(IV) chain is not a target antigen of anti-GBM nephritis. Nephritogenicity is apparently a property of α3–α5(IV)NC1.

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References

  1. Brazel D, Oberbäumer I, Dieringer H, Babel W, Glanville RW, Deutzmann R, Kühn K (1987) Completion of the amino acid sequence of the α1 chain of human basement membrane collagen (type IV) reveals 21 non-triplet interruptions located within the collagenous domain. Eur J Biochem 168: 529–536

    Google Scholar 

  2. Brazel D, Pollner R, Oberbäumer I, Kühn K (1988) Human basement membrane collagen (type IV). The amino acid sequence of the α2(IV) chain and its comparison with the α1(IV) chain reveals deletions in the α1(IV) chain. Eur J Biochem 172: 35–42

    Google Scholar 

  3. Butkowski R, Wieslander J, Wilson BJ, Barr JF, Noelken ME, Hudson BG (1985) Properties of the globular domain of type IV collagen and its relationship to the Goodpasture antigen. J Biol Chem 260: 3739–3747

    Google Scholar 

  4. Butkowski RJ, Langeveld JPM, Wieslander J, Hamilton J, Hudson BG (1987) Localization of the Goodpasture epitope to a novel chain of basement membrane collagen. J Biol Chem 262: 7874–7877

    Google Scholar 

  5. Gubler M-C, Knebelmann B, Beziau A, Broyer M, Pirson Y, Haddoum F, Kleppel MM, Antignac C (1995) Autosomal recessive Alport syndrome: immunohistochemical study of type IV collagen chain distribution. Kidney Int 47: 1142–1147

    Google Scholar 

  6. Hostikka SL, Tryggvason K (1988) The complete primary structure of the α2 chain of human type IV collagen and comparison with the α1(IV) chain. J Biol Chem 263: 19488–19493

    Google Scholar 

  7. Hostikka SL, Eddy RL, Byers MG, Höyhtya M, Shows TB, Tryggvason K (1990) Identification of a distinct type IV collagen α chain with restricted kidney distribution and assignment of its gene to the locus of X chromosome-linked Alport syndrome. Proc Natl Acad Sci USA 87: 1606–1610

    Google Scholar 

  8. Hudson BG, Kalluri R, Gunwar S, Noelken ME, Mariyama M, Reeders ST (1993) Molecular characteristics of the Goodpasture autoantigen. Kidney Int 43: 135–139

    Google Scholar 

  9. Kalluri R, Gunwar S, Reeders ST, Morrison KC, Mariyama M, Ebner KE, Noelken ME, Hudson BG (1991) Goodpasture syndrome: localization of the epitope for the autoantibodies to the carboxyl-terminal region of the α3(IV) chain of basement membrane collagen. J Biol Chem 266: 24018–24024

    Google Scholar 

  10. Kalluri R, Gattone VH II, Noelken ME, Hudson BG (1994) The α3 chain of type IV collagen induces autoimmune Goodpasture syndrome. Proc Natl Acad Sci USA 91: 6201–6205

    Google Scholar 

  11. Kishiro Y, Kagawa M, Naito I, Sado Y (1995) A novel method of preparing rat-monoclonal antibody-producing hybridomas by using rat medial iliac lymph node cells. Cell Struct Funct 20:151–156

    Google Scholar 

  12. Kleppel MM, Fan WW, Cheong HI, Kashtan CE, Michael AF (1992) Immunochemical studies of the Alport antigen. Kidney Int 41: 1629–1637

    Google Scholar 

  13. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685

    PubMed  Google Scholar 

  14. Leinonen A, Mariyama M, Mochizuki T, Tryggvason K, Reeders ST (1994) Complete primary structure of the human type IV collagen α4(IV) chain. J Biol Chem 269: 26172–26177

    Google Scholar 

  15. Mariyama M, Leinonen A, Mochizuki T, Tryggvason K, Reeders ST (1994) Complete primary structure of the human α3(IV) collagen chain: coexpression of the α3(IV) and α4(IV) collagen chains in human tissues. J Biol Chem 269: 23013–23017

    Google Scholar 

  16. Nakanishi K, Yoshikawa N, Iijima K, Kitagawa K, Nakamura H, Ito H, Yoshioka K, Kagawa M, Sado Y (1994) Immunohistochemical study of α1–5 chains of type IV collagen in hereditary nephritis. Kidney Int 46: 1413–1421

    Google Scholar 

  17. Neilson EG, Kalluri R, Sun MJ, Gunwar S, Danoff T, Mariyama M, Myers JC, Reeders ST, Hudson BG (1993) Specificity of Goodpasture autoantibodies for the recombinant noncollagenous domains of human type IV collagen. J Biol Chem 268: 8402–8405

    Google Scholar 

  18. Ninomiya Y, Kagawa M, Iyama K, Naito I, Kishiro Y, Seyer JM, Sugimoto M, Oohashi T, Sado Y (1995) Differential expression of two basement membrane collagen genes, COL4A6 and COL4A5 demonstrated by immunofluorescence staining using peptide-specific monoclonal antibodies. J Cell Biol 130: 1219–1229

    Google Scholar 

  19. Nishikawa K, Guo Y-J, Miyasaka M, Tamatani T, Collins AB, Sy M-S, McCluskey RT, Andres G (1993) Antibodies to intercellular adhesion molecule 1/Lymphocyte function-associated antigen 1 prevent crescent formation in rat autoimmune glomerulonephritis. J Exp Med 177: 667–677

    Google Scholar 

  20. Oohashi T, Sugimoto M, Matei M, Ninomiya Y (1994) Identification of a new collagen IV chain, α6(IV), by cDNA isolation and assignment of the gene to chromosome Xq22, which is the same locus for COL4A5. J Biol Chem 269: 7520–7526

    Google Scholar 

  21. Pusey CD, Holland MJ, Cashman SJ, Sinico RA, Lloveras J-J, Evans DJ, Lockwood CM (1991) Experimental autoimmune glomerulonephritis induced by homologous and isologous glomerular basement membrane in Brown-Norway rats. Nephrol Dial Transplant 6: 457–465

    Google Scholar 

  22. Sado Y, Watanabe K, Okigaki T, Takamiya H, Seno S (1984) Isolation and characterization of nephritogenic antigen from bovine glomerular basement membrane. Biochim Biophys Acta 798: 96–102

    Google Scholar 

  23. Sado Y, Okigaki T, Takamiya H, Seno S (1984) Experimental autoimmune glomerulonephritis with pulmonary hemorrhage in rats. The dose-effect relationship of the nephritogenic antigen from bovine glomerular basement membrane. J Clin Lab Immunol 15: 199–204

    Google Scholar 

  24. Sado Y, Naito I, Okigaki T (1989) Transfer of anti-glomerular basement membrane antibody-induced glomerulonephritis in inbred rats with isologous antibodies from the urine of nephritic rats. J Pathol (Lond) 158: 325–332

    Google Scholar 

  25. Sado Y, Kagawa M, Naito I, Okigaki T (1991) Properties of bovine nephritogenic antigen that induces anti-GBM nephritis in rats and its similarity to the Goodpasture antigen. Virchows Archiv [B] 60: 345–351

    Google Scholar 

  26. Sado Y, Kagawa M, Rauf S, Naito I, Moritoh C, Okigaki T (1992) Isologous monoclonal antibodies can induce anti-GBM glomerulonephritis in rats. J Pathol (Lond) 168: 221–227

    Google Scholar 

  27. Sado Y, Kagawa M, Kishiro Y, Sugihara K, Naito I, Seyer JM, Sugimoto M, Oohashi T, Ninomiya Y (1995) Establishment by the rat lymph node method of epitope-defined monoclonal antibodies recognizing the six different a chains of type IV collagen. Histochem Cell Biol 104: 267–275

    Google Scholar 

  28. Saus J, Wieslander J, Langeveld JPM, Quinones S, Hudson BG (1988) Identification of the Goodpasture antigen as the α3(IV) chain of collagen IV. J Biol Chem 263: 13374–13380

    Google Scholar 

  29. Soininen R, Haka-Risku T, Prockop DJ, Tryggvason K (1987) Complete primary structure of the α1-chain of human basement membrane (type IV) collagen. FEBS Lett 225: 188–194

    Google Scholar 

  30. Steblay RW (1962) Glomerulonephritis induced in sheep by injections of heterologous glomerular basement membrane and Freund's complete adjuvant. J Exp Med 116: 253–272

    Google Scholar 

  31. Sugihara K, Sado Y, Ninomiya Y, Wada Y (1996) Experimental anti-GBM glomerulonephritis induced in rats by immunization with synthetic peptides based on six α chains of human type IV collagen. J Pathol (Lond) 178: 352–358

    Google Scholar 

  32. Sugimoto M, Oohashi T, Ninomiya Y (1994) The genes COL4A5 and COL4A6, coding for basement membrane collagen chains α5(IV) and α6(IV), are located head-to-head in close proximity on human chromosome Xq22 and COL4A6 is transcribed from two alternative promoters. Proc Natl Acad Sci USA 91: 11679–11683

    Google Scholar 

  33. Wieslander J, Barr JF, Butkowski RJ, Edwards SJ, Bygren P, Heineg»rd D, Hudson BG (1984) Goodpasture antigen of the glomerular basement membrane: localization to noncollagenous regions of type IV collagen. Proc Natl Acad Sci USA 81: 3838–3842

    Google Scholar 

  34. Wieslander J, Langeveld J, Butkowski R, Jodlowski M, Noelken M, Hudson BG (1985) Physical and immunochemical studies of the globular domain of type IV collagen. Cryptic properties of the Goodpasture antigen. J Biol Chem 260: 8564–8570

    Google Scholar 

  35. Wieslander J, Barr JF, Butkowski RJ, Edwards SJ, Bygren P, Heineg»rd D, Hudson BG (1987) Goodpasture antigen of the glomerular basement membrane: localization to noncollagenous regions of type IV collagen. Proc Natl Acad Sci USA 262: 7874–7877

    Google Scholar 

  36. Wilson CB, Dixon FJ (1973) Anti-glomerular basement membrane antibody-induced glomerulonephritis. Kidney Int 3: 74–89

    Google Scholar 

  37. Zhou J, Hertz JM, Leinonen A, Tryggvason K (1992) Complete amino acid sequence of the human α5(IV) collagen chain and identification of a single-base mutation in exon 23 converting glycine 521 in the collagenous domain to cysteine in Alport syndrome patient. J Biol Chem 267: 12475–12481

    Google Scholar 

  38. Zhou J, Mochizuki T, Smeets H, Antignac C, Laurila P, Paepe A de, Tryggvason K, Reeders ST (1993) Deletion of the paired α5(IV) and α6(IV) collagen genes in inherited smooth muscle tumors. Science 261: 1167–1169

    Google Scholar 

  39. Zhou J, Ding M, Zhao Z, Reeders ST (1994) Complete primary structure of the sixth chain of human basement membrane collagen, α6(IV). J Biol Chem 269: 13193–13199

    Google Scholar 

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Rauf, S., Kagawa, M., Kishiro, Y. et al. Nephritogenicity and α-chain composition of NC1 fractions of type IV collagen from bovine renal basement membrane. Vichows Archiv A Pathol Anat 428, 281–288 (1996). https://doi.org/10.1007/BF00196702

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  • DOI: https://doi.org/10.1007/BF00196702

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