Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A radioimmunoassay for detection of antitubular basement membrane (TBM) antibodies was set up using a human TBM antigen (mol wt, 70,000 daltons), purified after collagenase treatment of the insoluble membrane by preparative polyacrylamide electrophoresis, and labeled with iodine 125. Free labeled antigens were separated from those bound to immunoglobulins by a 20% polyethylene glycol (mol wt, 6,000 daltons) solution. In the presence of normal human or Brown Norway rat sera, less than 10% of the labeled antigens were precipitated. In the presence of sera or of kidney eluates from rats immunized with human TBM, the precipitation of the labeled TBM antigens reached 73%, but in the presence of sera from two patients presenting with an interstitial nephritis and linear deposits along the TBM only, up to 47% of the same antigens were precipitated. In these two cases, the anti-TBM antibodies were mainly directed against the heteropolysaccharide-containing glycopeptides isolated from TBM, that is, against the noncollagenous polypeptides of the TBM antigens. Anti-TBM antibodies were sought in the sera of 52 normal blood donors and of 11 patients presenting with glomerulonephritis and linear deposits of immunoglobulins. The average percentage (+/- 1 SD) of labeled TBM antigens precipitated in the serum of normal blood donors was 7.1 +/- 1.2. Of the patients presenting with glomerulonephritis and linear deposits along the GBM, 9 out of 11 exhibited anti-TBM antibodies by radioimmunoassay; among these 9 patients, 8 also displayed linear deposits of IgG along the TBM. Absorption of anti-TBM and anti-GMB antibodies with particulate TBM or GBM, with both types of glycopeptides isolated from GBM or TBM, indicated that the anti-TBM antibodies were directed against the noncollagenous polypeptides of TBM but that the anti-GBM antibodies mainly reacted with the collagenous polypeptides of TBM and GBM. Finally, it was found that the sera of 2 patients out of 15 presenting with lupus nephritis contained a significant anti-TBM-binding activity, mainly directed against the noncollagenous material of TBM.
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PMID:Radioimmunologic method for detection of antitubular basement membrane antibodies. 74 71

The target antigen, a 54-kD glycoprotein (gp54), reactive with sera from patients with anti-tubular basement membrane (anti-TBM) nephritis, was isolated from collagenase-digested (CD) bovine TBM. The purified gp54 was shown to be non-collagenous by amino acid analysis, and to be a unique basement membrane component by amino-terminal sequencing. The nephritogenicity of gp54 was demonstrated by immunizing strain XIII guineapigs with purified gp54, and producing anti-gp54 antibody and tubulo-interstitial nephritis. Anti-gp54 antibody, affinity-purified from sera of patients with anti-TBM nephritis, bound by immunoblotting to 54-kD and, to a lesser extent, 48-kD components of partially purified human CD-TBM. Indirect immunofluorescence showed that gp54 was present in the basement membrane of proximal tubules of the kidneys of normal human, cow, rabbit, guineapig and Brown-Norway rat but not in Lewis rat. Immunoelectron microscopy revealed localization of gp54 along the interstitial side of the TBM and its association with interstitial collagen fibres. These results indicate that gp54 is the nephritogenic antigen involved in tubulo-interstitial nephritis, and is unique in chemical characteristics and localization in the kidney.
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PMID:Isolation and characterization of the tubular basement membrane antigen associated with human tubulo-interstitial nephritis. 142 91

In order to study disease mechanisms and potential forms of therapy in glomerulonephritis, a model of experimental autoimmune glomerulonephritis (EAG) has been developed in the rat. We have examined the response of Brown-Norway (BN) rats to a single i.m. injection of collagenase-solubilised homologous (Sprague-Dawley, SD) or isologous (BN) glomerular basement membrane (GBM), with and without complete Freund's adjuvant (CFA). There was a dose-dependent circulating anti-GBM antibody response to all preparations of rat GBM. Animals given either antigen alone at a dose of 2 mg/kg developed circulating anti-GBM antibodies, which reached peak values by 6 weeks (63 +/- 5% following SD GBM; 53 +/- 8% following BN GBM), but did not develop glomerular deposits of IgG or nephritis. Animals given 2 mg/kg SD GBM in CFA developed greater concentrations of anti-GBM antibody by 6 weeks (122 +/- 20%) together with linear deposits of IgG on glomerular and tubular basement membranes (TBM), albuminuria (mean 7 mg/24 h), and variable focal segmental necrotising glomerulonephritis with mild interstitial nephritis. The same dose of BN GBM in CFA produced similar concentrations of circulating antibody (144 +/- 26%), with linear deposits of IgG on GBM but rarely TBM, little albuminuria, and variable mild focal glomerulonephritis. Other strains injected with SD GBM in CFA showed a variable circulating anti-GBM antibody response, which was similar to that of BN rats in PVG and DA rats but lower in LEW and WAG rats. Linear deposits of IgG on the GBM were detected in a proportion of PVG and DA rats, but not in LEW or WAG rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimental autoimmune glomerulonephritis induced by homologous and isologous glomerular basement membrane in Brown-Norway rats. 192 7

Tubular basement membrane (TBM) was prepared from normal human kidneys and solubilized with various enzymes. Collagenase digestion released antigenic moieties from the TBM. All four anti-TBM antibodies we studied, three from patients with idiopathic tubulo-interstitial nephritis (TIN) and one from a renal allograft recipient, distinctively reacted with collagenase-digested (CD) TBM during enzyme-linked immunoassay and could discriminate among sera of normal controls or of other nephritis patients, including anti-glomerular basement membrane (anti-GBM) nephritis. When digested with pronase, trypsin, or pepsin, antigenicity of the TBM decreased. We studied the TBM antigens with immunoprecipitation and immunoblotting. After incubation of radio-iodinated CDTBM with anti-TBM sera, immunoprecipitates were identified by single-dimension SDS polyacrylamide gel electrophoresis or two-dimension gel electrophoresis, followed by autoradiography. All four antibodies had identical results on immunoprecipitation; under nonreducing conditions, they gave two protein bands with m.w. of 54,000 and 48,000 and with pI 7.0 to 8.0 and 6.5 to 7.0. Electrophoresis performed under reducing conditions disclosed only one band at the m.w. of 48,000 and pI of 6.5, suggesting that the 54-kDa component is composed of peptides linked by interchain disulfide bonds. Immunoblot analysis showed that the anti-TBM antibodies were heterogeneous; three antibodies from the idiopathic TIN patients reacted with the 54-kDa band, but the one from the renal allograft recipient reacted with neither band. This finding suggests that there are two antigenic determinants on the 54-kDa component. One such determinant that was resistant to denaturation with SDS was detected by the first three antibodies, and the other that was sensitive to such denaturation bound to the last antibody. The 48-kDa component seemed not to be immunoreactive after incubation with SDS. We studied TBM antigens reactive with anti-GBM antibodies. By immunoblotting, all four sera from patients with anti-GBM nephritis stained TBM proteins of 45 to 50 kDa and 25 to 27 kDa at pH 8.0 to 9.0; this was similar to the staining pattern of CDGBM with the same sera, but the highly cationic (pH greater than 9.0) components were specifically detected in the CDGBM. By inhibition ELISA, the binding of the anti-GBM sera to denatured CDTBM decreased with preincubation of the sera with CDGBM, suggesting that the anti-GBM antibodies recognize the same epitope(s) on the GBM and the TBM.
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PMID:Characterization of tubular basement membrane antigens in human kidney. 300 98

Proximal tubular epithelial cells from mice which develop autoimmune interstitial nephritis were found to express the nephritogenic target antigen, 3M-1. Anti-3M-1 mAbs (alpha 3M-1-Ab) were used to positively select for 3M-1-secreting tubular epithelium and, after stabilization in culture, this new cell line (MCT) was examined for the production of several moieties important to either immune interactions or to the development of extracellular matrix. Alkaline phosphatase-staining MCT cells also express epithelial growth factor receptors with a Kd of 0.87 nM and an epithelial growth factor receptor constant (Ro) of 2.1 X 10(4) receptors/cell. MCT culture supernatants contain greater amounts of laminin, and types IV and V procollagens compared to types I and III procollagens, and growing MCT cells on type I collagen matrix causes them to preferentially secrete even more type IV and V procollagen. The 30,000-Mr 3M-1 antigen could be immunoprecipitated from biosynthetically labeled MCT cell supernatants with alpha 3M-1-Ab. An identical-sized moiety was isolated by immunoaffinity chromatography from collagenase-solubilized mouse kidney tubular basement membranes. The 3M-1 antigen can be found on the MCT cell surface by radioimmunoassay, or deposited in a linear array in the extracellular matrix surrounding the MCT cells in culture by immunofluorescence. Mature messenger RNA species for both class I and class II major histocompatibility complex (MHC) molecules were detected by Northern hybridization, and their corresponding cell surface gene products were detected by cytofluorography of MCT cells stained with haplotype-specific antibodies. Both the cell surface 3M-1 and the small amounts of detected class II MHC molecules appear to be biologically functional, as MCT cells can support the proliferation of 3M-1-specific, class II MHC-restricted helper T cells in culture. These findings suggest that MCT cells provide all the necessary biological parameters for interfacing both as the target of a nephritogenic immune response, and as a potential source for new extracellular matrix which develops as a fibrogenic response to interstitial nephritis.
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PMID:Characterization of a renal tubular epithelial cell line which secretes the autologous target antigen of autoimmune experimental interstitial nephritis. 317 Jun 33

Using a monoclonal anti-tubular basement membrane antibody (alpha TBM-Ab) affinity column, we isolated from collagenase-solubilized human renal tissue (HSRTA) a predominantly 48,000-mol-wt moiety (H3M-1) which is selectively recognized by antisera from two patients with alpha TBM-Ab-associated interstitial nephritis (alpha TBM disease). Whereas both antisera had alpha TBM-Ab titers of 1:64-1:128 by immunofluorescence on tissue sections, their reactivity with H3M-1 in a solid-phase radioimmunoassay was demonstrable at dilutions up to 1:10,000. While these sera displayed some reactivity with pre-column HSRTA, this was markedly less than with H3M-1. HSRTA depleted of H3M-1 by passage over the alpha TBM-Ab affinity column was almost completely depleted of reactivity. Neither pooled normal human sera nor sera from patients with a variety of renal lesions not associated with alpha TBM-Ab (including interstitial nephritis and antiglomerular basement membrane disease) were reactive with H3M-1. Both patient antisera containing alpha TBM-Ab were also highly reactive with R3M-1, the 48,000-mol-wt rabbit glycoprotein antigen of experimental alpha TBM disease. Furthermore, a competitive inhibition radioimmunoassay revealed that alpha TBM-Ab from rodents with experimental alpha TBM disease could inhibit 45-98% of the R3M-1 binding reactivity of patient antisera and 85% of the H3M-1 binding reactivity of patient antisera, thus suggesting paratypic cross-reactivity. We conclude, therefore, that tubular basement membrane target epitopes and their paratypic recognition are highly conserved among mammals.
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PMID:Isolation of the target antigen of human anti-tubular basement membrane antibody-associated interstitial nephritis. 351 74

Using monoclonal antibody affinity chromatography, we isolated a 48,000 mol wt, glucose-rich glycoprotein (3M-1) from collagenase-solubilized rabbit renal tubular basement membrane (SRTA). The purified 3M-1 protein is noncollagenous, and is capable of inducing anti-TBM (tubular basement membrane) antibodies and interstitial nephritis in susceptible hosts. Further, when SRTA, at a normally nephritogenic dose, was selectively depleted of 3M-1, it lost its ability to induce disease. As shown by immunofluorescent techniques, 3M-1 appears to be localized on rodent TBM to the exclusion of the glomerular basement membrane, but was lacking in the TBM of the LEW rat, a strain devoid of the relevant antigen of anti-TBM disease. Immunoelectron microscopy revealed that 3M-1 was associated with the most lateral aspect of the TBM, which borders, and lies in the interstitium. These results indicate that 3M-1 is the nephritogenic antigen producing experimental anti-TBM disease.
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PMID:Isolation and characterization of the nephritogenic antigen producing anti-tubular basement membrane disease. 388 78

Our previous studies showed that 54 kD and 48 kD tubular basement membrane (TBM) proteins were the major form of the target antigen involved in anti-TBM antibody-mediated tubulo-interstitial nephritis in humans. In those studies, we isolated the 54 kD glycoprotein (named gp54) from collagenase-digested bovine TBM. NH2-terminal amino acid sequencing indicated that gp54 represented a newly defined glycoprotein. In this study, we further characterized the target antigen, using mouse monoclonal antibodies to gp54 and polyclonal anti-gp54 peptide antibody. Two monoclonal antibodies (H79 and H80) were established, and they reacted, by immunofluorescence, predominantly with the proximal TBM of humans, rabbits, and Wistar, Sprague-Dawley, and Brown-Norway rats, but not with that of Lewis rats. They were also fixed by blotting intensely to the 54 kD component and weakly to the 48 kD component of collagenase-digested human TBM. In vivo transfer of H79 to Wistar rats showed extensive linear binding of mouse IgG to the TBM and the basal membrane of the small intestine; however, no pathologic changes were seen by light microscopy. The anti-gp54 peptide antibody reacted with both the 54 kD and 48 kD TBM components of human TBM. mRNA was prepared from rabbit kidneys, and fractionated to enrich mRNA encoding the 54 kD and 48 kD peptides. On in vitro translation experiments with the mRNA fraction, the 54 kD and 48 kD peptides were immunoprecipitated with anti-gp54 antibodies. These findings indicate that the 54 kD and 48 kD components are encoded with different mRNA, but that they share the same antigenic epitope.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The target antigen of anti-tubular basement membrane antibody-mediated interstitial nephritis. 785 11

kdkd mice, a mutant subline of CBA/Ca mice, develop a progressive, T cell-mediated, autoimmune interstitial nephritis which leads to renal failure and death of all mice at 20-28 weeks of age. This disease is inherited in an autosomal recessive manner, with complete penetrance, and has been linked to grizzled and waltzer on mouse chromosome 10. Immunologic evaluation of this lesion has demonstrated that histologic disease is initiated by a population of CD8+, H-2Kk-restricted T cells, which recognize an antigen in collagenase-solubilized syngeneic renal tubules. These nephritogenic effector cells can also be demonstrated in non-disease prone CBA/Ca mice. Susceptibility to autoimmune nephritis correlates with distinct expression of regulatory, rather than effector, T cells. Interstitial nephritis in kdkd mice can be inhibited by protein-calorie restriction, infusions of CBA/Ca CD8+ T cells, or monoclonal antibodies of ICAM-1. This murine model most closely resembles medullary cystic disease in humans, which has not historically been considered an autoimmune disease. Mapping of the genes for both medullary cystic disease and the defect in kdkd mice should augment our understanding of mechanisms of organ-specific autoimmunity.
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PMID:Inherited interstitial nephritis in kdkd mice. 793 Aug 48

Some forms of glomerulonephritis (GN) in humans appear consequent to autoimmunity. Experimental autoimmune GN (EAG) has been described in sheep, but attempts to develop EAG in other mammals have resulted only in antibody and proteinuria but no GN. We have developed a model of EAG in an inbred mammalian species to further study pathogenetic mechanisms. We immunized Brown Norway (BN) and Wistar-Kyoto (WKY) rats with glomerular basement membrane (GBM) or collagenase solubilized GBM (csGBM). Circulating and bound anti-GBM antibody developed in all rats. Only interstitial nephritis occurred in BN rats despite amounts of glomerular and serum anti GBM antibodies similar to WKY animals. One hundred percent of WKY rats immunized with csGBM/acid developed reproducible severe GN at two to three weeks with proteinuria and decreased kidney function which progressed to glomerulosclerosis and interstitial fibrosis. Antigen in acid was a requisite for induction of EAG. EAG rats had positive tests for delayed type hypersensitivity, their T cells underwent antigen specific transformation, and T cells and macrophages were present histologically. Passive transfer of EAG serum to naive rats resulted in fixation to recipient GBM but no proteinuria or GN. This new model of EAG in rats appears dependent on genetic factors, may involve cellular immunity in pathogenesis, requires exposure of the nephritogenic antigen, and is highly similar to rapidly progressive GN in humans.
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PMID:Proliferative autoimmune glomerulonephritis in rats: a model for autoimmune glomerulonephritis in humans. 837 73


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