Abstract
The possible involvement of basement membrane-associated collagen (recognized by the monoclonal antibody JK-132) in the evolution of diabetic nephropathy was studied in kidney specimens from seven patients with noninsulin-dependent diabetes mellitus, and its distribution was compared with those of antibodies against α1 to α4 chains of type IV collagen. JK-132, a monoclonal antibody against basement membrane-associated collagen, reacted immunohistochemically exclusively with the mesangial matrix of the glomerular capillary. In contrast, antibodies to the α1 and α2 chains (IV) reacted strongly with mesangial matrix, and less strongly with the glomerular basement membrane (GBM). Antibodies to the α3 and α4 chains (IV) reacted mainly with GBM. In diabetes, JK-132 reacted most extensively with the expanded mesangial matrix, its staining intensity increasing with progression of the diabetic glomerulosclerosis. Antibodies to the α1 and α2 chains (IV) reacted prominently with the expanded mesangial matrix but less strongly with the GBM. Antibodies to the α3 and α4 chains reacted intensely with the thickened GBM. These results suggest that basement membrane-associated collagen differs from α1 to α4 chains of type IV collagen and that basement membrane-associated collagen is a good marker of mesangial expansion in diabetic nephropathy.
Similar content being viewed by others
References
Adachi E, Kino J, Hayashi T, Sato Y, Hashimoto PH (1989) The effect of fixatives and paraffin embedding on the histochemical reactivity of a monoclonal antibody against human type IV collagen (JK-199). Arch Histol Cytol 52:477–483
Beisswenger PJ, Spiro RG (1973) Studies on the human glomerular basement membrane: composition, nature of the carbohydrate units, and chemical changes in diabetes mellitus. Diabetes 22:180–193
Brazel D, Polner RR, Oberbaumer I, Khn 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. Eur J Biochem 172:35–42
Butokowski RJ, Wieslander J, Wisdom B, 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
Butokowski RJ, Langevelt 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
Butokowski RJ, Wieslander J, Klepel M, Michael AF, Fish AJ (1989) Basement membrane collagen in the kidney: regional localization of novel chains related to collagen IV. Kidney Int 35:1195–1202
Chu ML, Weil D, de West W, Bernard M, Sippola M, Ramirez F (1985) Isolation cDNA and genomic clones encoding human pro-α1 (III) collagen. J Biol Chem 260:4357–4363
Falk RJ, Scheinman JI, Mauer SM, Michael AF (1983) Polyantigenic expansion of basement membrane constituents in diabetic nephropathy. Diabetes 32:24–39
Fouser LS, Michael AF (1987) Antigens of the human glomerular basement membrane. Springer Semin Immunopathol 9:317–339
Gellman DD, Pirani CL, Soothhill JF, Muehrocke RC, Kark RM (1959) Diabetic nephropathy. A clinical and pathogenic study based on renal biopsies. Medicine (Baltimore) 38:321–367
Griffin CA, Emanuel BS, Hansen JR, Cavenee WK, Myers JC (1987) Human collagen genes encoding basement membrane α1 (IV) and α2 (IV) chains map to the distal long arm of chromosome 13. Proc Natl Acad Sci USA 84:512–516
Gunwar SG, Saus J, Noelken ME, Hudson BG (1990) Glomerular basement membrane. Identification of a fourth chain α4 of type IV collagen. J Biol Chem 265:5466–5469
Hostetter TH (1991) Diabetic nephropathy. In: Brenner BM, Rector FC (eds) The Kidney. Saunders Philadelphia pp 1695–1727
Hostikka SL, Eddy RL, Byers MG, Hoyhtya M, Shows TB, Tryggvason K (1990) Identification of a distinct type IV collagen 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
Hudson BG, Wieslander J, Wisdom BJ, Noelken ME (1989) Biology of disease. Goodpasture syndrome: molecular architecture and function of the basement membrane antigen. Lab Invest 61:256–269
Ihm CG, Lee GSL, Nast CC, Artishevsky A, Guillermo R, Levin PS, Glassock RJ, Adler S (1992) Early increased renal procollagen α1 (IV) mRNA levels in streptozotocin induced diabetes. Kidney Int 41:768–777
Johanasson C, Butokowski R, Wieslander J (1991) Characterization of monoclonal antibodies to the globular domain of collagen IV. Connect Tissue Res 25:229–241
Kanwar YS (1984) Biophysiology of glomerular filtration and proteinuria. Lab Invest 51:7–21
Karttunen T, Risteli J, Autio-Harmainen H, Ristali L (1986) Effect of age and diabetes on type IV collagen and laminin in human kidney cortex. Kidney Int 30:586–591
Kashtan C, Fish AJ, Kleppel M, Yoshioka K, Michael AF (1986) Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis. J Clin Invest 78:1035–1044
Kleppel MM, Santi PA, Cameron JD, Wieslander J, Michael AF (1989) Distribution of familial nephritis antigen in normal tissue and renal basement membranes of patients with homozygous and heterozygous Alport familial nephritis. Relationship of familial nephritis and Goodpasture antigens to novel collagen chains and type IV collagen. Lab Invest 61:278–289
Kim Y, Butokowski R, Burke B, Kleppel MM, Crosson J, Katz A, Michael AF (1991a) Differential expression of basement membrane collagen in membranous nephropathy. Am J Pathol 139:1381–1388
Kim Y, Kleppel MM, Butokowski R, Mauer SM, Wieslander J, Michael AF (1991b) Different expression of basement membrane collagen chains in diabetic nephropathy. Am J Pathol 138:413–420
Kino J, Adachi E, Yoshida T, Nakajima K, Hayashi T (1988): Characterization of a monoclonal antibody against human placenta type IV collagen by immunoelectroblotting, antibody-coupled affinity chromatography, and immunohistochemical localization. J Biochem 103:829–835
Kino J, Adachi E, Yoshida T, Asamatsu C, Nakajima K, Yamamoto K, Hayashi T (1991) A novel chain of basement membrane associate collagen as revealed by biochemical and immunohistochemical characterizations of the epitope recognized by a monoclonal antibody against human placenta basement membrane collagen. Am J Pathol 138:911–920
Langeveld JPM, Wieslander J, Timoneda J, McKinney P, Butkowski RJ, Wisdom B, Hudson BG (1988) Structural heterogeneity of the noncollagenous domain of basement membrane collagen. J Biol Chem 263:10481–10488
Ledbetter S, Copeland EJ, Noonan D, Vogeli G, Hassell JR (1990) Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thoromboxane synthesis inhibition. Diabetes 39:196–203
Makino H, Gibbons JT, Reddy MK, Kanwar YS (1986) Nephritogenicity of antibodies to proteoglycans of the glomerular basement membrane — 1. J Clin Invest 77:142–156
Makino H, Yamasaki Y, Haramoto T, Shikata K, Hironaka K, Ota Z, Kanwar YS (1993) Ultrastructural changes of extracellular matrices in diabetic nephropathy revealed by high resolution scanning and immunoelectron microscopy. Lab Invest 68:45–55
Mariyama M, Zheng K, Yang-Feng T, Reeders ST (1992) Colocalization of the genes for the α3 (IV) and α4 (IV) chains of type IV collagen to chromosome 2 bands q35–q37. Genomics 13:809–813
Meyers JC, Loid HR, Seyer JM, Dion AS (1985) Complete primary structure of the human α2 type V procollagen. J Biol Chem 260:4357–4363
Muthkumaran G, Blumberg B, Kurkinen M (1989) The complete primary structure for the α1-chain of mouse collagen IV. J Biol Chem 264:6310–6317
Nerlich A, Schleichert E (1991) Immunohistochemical localization of extracellular matrix components in diabetic glomerular lesions. Am J Pathol 139:889–89939
Ninomiya Y, Gordon M, Van der Rest M, Schmid T, Lisenmayer T, Olsen BR (1985) The developmentally regulated type X collagen gene contains a long open reading frame without introns. J Biol Chem 261:5041–5050
Olson JL (1992) Diabetes mellitus. In: Heptinstall RH (ed) Pathology of the Kidney. Little, Brown & Co., Boston, pp 1715–1763
Poschel E, Pollner R, Kuhn K (1988) The genes for the α1 (IV) and α2 (IV) chains of human basement collagen type IV are arranged head-to-head and separated by a bidirectional promoter of unique structure. EMBO J 7:2687–2695
Saou J, Quinoes S, Mackrell K, Blumberg B, Muthukumaran G, Pihlajaniemi T, Kurkinen M (1989) The complete primary structure of mouse α (IV) collagen. J Biol Chem 264:6318–6324
Saus J, Wieslander J, Langevelt 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
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
Timpl R, Aumailley M (1989) Biochemistry of basement membranes. In: Grunfeld JP, Funck-Brentano JL, Maxwell MH (eds.) Advances in Nephrology, Year Book Medical Publishers, Chicago, 18:59–76
Van der Rest M, Mayme R, Ninomiya Y, Seidah NG, Chretien M, Olsen BR (1985) The structure of type IX collagen. J Biol Chem 260:220–225
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Makino, H., Shikata, K., Haramoto, T. et al. Immunoreactivity of the JK-132 monoclonal antibody directed against basement membrane collagen in normal and diabetic glomeruli. Vichows Archiv A Pathol Anat 424, 235–241 (1994). https://doi.org/10.1007/BF00194606
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00194606