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)

Antibodies to collagenous and noncollagenous components of glomerular basement membrane (GBM) have been detected by immunoblotting in some sera from patients with various kinds of glomerulonephritis. A half proportion of patients with rapidly progressive glomerulonephritis (RPGN), chronic focal glomerulonephritis (CFGN), idiopathic membranous glomerulonephritis (MGN). IgA nephropathy and lupus nephritis (LE-GN) had IgG antibodies to heterogenous components in acid insoluble fraction of pepsin digested GBM. This acid insoluble fraction represented a complex of collagen and noncollagenous proteins of GBM. Following digestion of acid insoluble fraction with bacterial collagenase, the triple helical collagenous components of GBM were destroyed and released most likely of noncollagenous proteins. Antibodies to this noncollagenous proteins were found in only some patients with chronic glomerulonephritis (17.6%) and lupus nephritis (21.4%). Upon reaction with human placenta derived type IV collagen, different frequencies of antibody response were found in patients of different groups. However, all these reactive sera showed a similar immunoblotting pattern. The relationship between antibody response to antigenic components from human GBM or human placenta and pathogenesis of renal disease is unclear. However, the occurrence of spontaneous autoantibody response to some exposed GBM self antigens may mediate further renal destruction resulting in chronic ongoing stage of the disease.
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PMID:Heterogeneity of antibody response to glomerular basement membrane antigen in patients with different forms of glomerulonephritis. 140 75

Two antibody probes were used to characterize the putative renal antigens of HgCl2-induced antiglomerular basement membrane renal disease in Brown Norway (BN) rat. The first probe was the linear immunofluorescence imparting, in vivo bound, nephritogenic antiglomerular-basement-membrane autoantibody (anti-GBM-Ab). The second probe was a rat monoclonal antibody to the B subunit of laminin that was obtained from fusion of spleen cells of HgCl2 injected BN rat. By enzyme-linked immunosorbent assay (ELISA) the anti-GBM-Ab reacted with laminin, type IV collagen, collagenase-resistant noncollagenous portion of glomerular basement membrane (GBM), saline soluble proteins of kidney cortex homogenate and fibronectin. Western blot analysis of laminin indicated that the reactive epitopes detected by both probes were on the B chain subunit but not the A subunit. In nonreduced collagenase-digested GBM the epitopes were present on 27 kD and 42 to 48 kD polypeptides. A similar pattern was seen on collagenase-digested human GBM. On rat and human GBM the patterns obtained with rat autoantibody and autoantibody from a patient with Goodpasture syndrome were similar, suggesting that some of the in vivo bound anti-GBM autoantibodies in HgCl2-induced disease in rat are directed against epitopes which are similar to the Goodpasture antigen of human. Reactive epitopes were also detected on saline soluble proteins of kidney cortex homogenate with the predominant antigen being a 31 kD polypeptide. In the saline soluble proteins the reactive polypeptides including the major 31 kD polypeptide did not originate from laminin, type IV collagen, or the collagenase-resistant noncollagenous part of GBM. The precise structural origin of soluble proteins was not defined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal antigens in mercuric chloride induced, anti-GBM autoantibody glomerular disease. 168 61

Experimental animal models of glomerulonephritis (GN) produced by direct antibody binding to non-basement membrane glomerular capillary wall antigens do not to date have human parallels. To examine the potential for this form of humoral glomerular injury in man, we sought to define discrete human non-GBM glomerular antigenic targets using hybridoma technology. Mice were immunised intraperitoneally with 20-100 micrograms of a human glomerular membrane fraction (HGMF). Six fusions have yielded 12 stable reagents defined by positive glomerular indirect immunofluorescence (IF) and microELISA using HGMF as the screening antigen. Subclass analysis of ascitic McAbs indicated several IgG1, one IgG2b, and three IgM reagents. Distinctive IF patterns of reactivity with epithelial, endothelial or mesangial structures have been observed, with or without peritubular capillary, tubular basement membrane and vessel wall reactivity. Seven normal non-renal human organs and the kidneys of rat, rabbit and sheep have shown patterns characteristic of each individual McAb, restricted to human or with species cross reactivity. To partially characterise McAb-reactive antigens, detergent-solubilised renal cortex and collagenase-solubilised GBM (CS-GBM) extracts have been probed by immunoblot. A unique McAb 7-5Q, reactive with glomerular and tubular epithelial structures, binds major bands of approximately 107 KD and 93 KD in detergent solubilised cortex and a single band of similar size by immunoprecipitation (110 KD). 5-3A (a human-restricted linear-reacting McAb) binds bands of 20-200 KD (major band 58 KD) in CS-GBM. In conclusion, distinct species-restricted and more broadly disposed glomerular epitopes are definable in man by McAbs and are potential targets for humoral injury. Purification of these antigens will allow assay for circulating putative nephritogenic auto-antibody and potentially, McAbs may be useful in screening urine for evidence of occult structural renal disease.
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PMID:Definition of glomerular antigens by monoclonal antibodies produced against a human glomerular membrane fraction. 170 58

The sera of 206 consecutive patients with biopsy-proven glomerulonephritis were tested by ELISA for the presence of Goodpasture and non-Goodpasture anti-GBM antibodies. Antigens were solubilised from human GBM with purified bacterial collagenase and with 6 mol/l guanidine-HCl respectively. Only 12 sera reacted when collagenase-resistant GBM proteins were used as antigens in ELISA. Sera from two of these patients also reacted with the Goodpasture antigen, that is the globular domain of collagen IV, purified from collagenase extracts of GBM. These two patients had classical Goodpasture syndrome with linear crescentic nephritis. The other ten sera did not react with the Goodpasture antigen and immunofluorescence microscopy showed granular glomerular immune deposits. Antibodies against antigens present in 6 mol/l guanidine-HCl extracts of human GBM were much more frequent, particularly in lupus nephritis and IgA nephropathy, but relatively common also in patients with glomerulonephritis associated with systemic connective tissue and systemic vasculitic disorders. In contrast, these non-Goodpasture antibodies were only sporadic in primary forms of glomerulonephritis such as minimal-change nephropathy, membranous glomerulopathy, or acute post-infectious glomerulonephritis. The presence of circulating IgG, IgA or IgM antibodies against 6 mol/l guanidine-HCl extractable GBM antigens correlated with granular deposits of corresponding immunoglobulins in both mesangial and capillary loop regions of glomeruli, indicating a possible pathogenic role for non-Goodpasture anti-GBM antibodies in several forms of glomerulonephritis.
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PMID:Non-Goodpasture anti-GBM antibodies in patients with glomerulonephritis. 250 32

The mixed lymphocyte kidney culture (MLKC) in humans has been studied in normal and abnormal clinical conditions. Human renal cortical cells were extracted by collagenase treatment from the kidneys of "normal" heart-beating cadaver organ donors (n = 13), patients with end-stage renal disease (ESRD) at pretransplant bilateral nephrectomy and splenectomy (n = 13), and from irreversibly rejected renal allografts at the time of graft nephrectomy (n = 5). Proliferation of peripheral blood T lymphocytes of 2-DR-mismatched volunteers occurred in response to kidney cortical cells extracted from each of the 3 donor categories in a reaction termed the allogeneic mixed lymphocyte kidney culture. Additionally, splenic T cells from cadavers and patients with ESRD were seen to react to their autologous kidney cells. The renal cortical cells extracted from ESRD kidneys were more stimulatory in the allogeneic and autologous MLKC responses than those extracted from "normal" cadaver kidneys even when the ESRD kidneys were 99% depleted of passenger T and B lymphocytes by treatment with monoclonal antibodies T11 and B1. In order to help define the antigens operative in the MLKC, we pretreated stimulating lymphocytes and renal cortical cells with anti-class II monoclonal antibodies. The allogeneic mixed lymphocyte reaction and MLKC were inhibited ca. 80% and 30%, respectively. The autologous MLKC was unaffected by this treatment. To further support that tissue-specific immune mechanisms were operative in the reaction, experiments were performed with infiltrating lymphocytes isolated from the ESRD kidneys, which were seen to generate a proliferative response when stimulated with autologous cortical cells. However, the response of these same infiltrating lymphocytes when stimulated with allogeneic lymphocytes (MLR), was markedly weaker than the response of the patients' autologous spleen cells. In addition, two kidneys were obtained at rejection from recipients that had received grafts from HLA-MLR-identical sibling donors. A lymphoproliferative reaction of recipient peripheral blood T lymphocytes occurred in response to (donor) renal cortical cells, but not to donor peripheral blood lymphocytes. In contrast, infiltrating (recipient) kidney lymphocytes responded to the kidney cortical cells and to donor peripheral blood lymphocytes. Moreover, peripheral blood T lymphocytes of the HLA-identical donor responded to his own kidney cortical cells, which were isolated from the rejected recipient kidney, and did not respond to recipient peripheral blood lymphocytes. Finally, a "normal" cadaveric kidney was fortuitously available at the same time that a rejected transplant (cadaver)
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PMID:The biologic significance of the mixed lymphocyte kidney culture in humans. 299 86

The specificity in the mixed lymphocyte kidney culture (MLKC) of T cell lines and clones derived from human end-stage renal disease (ESRD) kidneys was studied using collagenase dispersed kidney cells compared with lymphocytes as stimulating cells. These experiments were performed because of previous studies in which infiltrating lymphocytes freshly isolated from ESRD kidney tissue at nephrectomy (as well as autologous splenic T cells) were seen to directly generate this lymphoproliferative MLKC response when stimulated with autologous renal cortical cells. In the current studies, histopathologic staining of tissues and suspensions of infiltrating kidney lymphocytes showed predominance of OKT4 labeled phenotypes, and the stimulation indices in MLKC in general showed a direct relationship with the percentage of helper cells seen in the infiltrates. When T cell lines and clones derived from lymphocytes infiltrating the ESRD kidneys were tested in MLKC, there was evidence of kidney-associated, as opposed to lymphocyte-associated (MLC) reactivity using (3H) thymidine uptake as a reflection of a lymphoproliferative response. Several cell lines and clones derived from these T lymphocytes exhibited a dual reactivity. They served as responding cells in the MLKC reaction and completely suppressed a non-specific allogeneic MLC when added as third-party cells. Quantitatively, some clones suppressed when third-party x-irradiated cells were only 5% of the responding cell number in coculture. In addition to the dual reactivity, phenotypic analysis of these same cell lines and clones employing monoclonal antibodies revealed that individual cells expressed both OKT4 and OKT8 determinants. However, approximately 90% of the cells in the MLC enhancing line were labeled with OKT4. These results indicate that there is a complexity in the autologous MLKC response in that cells with both helper/inducer and suppressor/cytotoxic function take part in the reaction. Although delayed-type hypersensitivity to kidney-associated antigens is inferred as a result of these in vitro assays, nonspecific suppression of other Ia-dependent reactions can simultaneously occur.
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PMID:T cell lines and clones preferentially recognizing kidney-associated antigens in end-stage renal disease. 300 32

Urinary excretion of glomerular basement membrane (GBM)-related peptides was analysed in 72 patients with a variety of renal diseases by immunoblotting using polyclonal antibodies against either collagenase or pepsin digests of human GBM. The specificity of the antibodies was verified by elution of antibodies bound to urinary GBM-related peptides on nitrocellulose blots and demonstration of reactivity of the eluted antibodies with the respective GBM digests. Furthermore, six mice immunized with urinary GBM-related peptides all developed focal linear deposits of mouse IgG along their GBM, linear and mesangial deposits of C3 in the glomeruli and serum antibodies reactive with human GBM. Monoclonal antibodies against urinary GBM-related peptides of one of the mice reacted with different peptides of the non-collagenous and collagenous domains of type IV collagen, the major structural protein of GBM. In the majority of the 75 patients' urines tested, excretion of GBM-related peptides with molecular weights of 33, 50, 80 and 150 kilodaltons (kD) was detectable. Patients with a diminished glomerular filtration rate (GFR) demonstrated excretion of the 33 kD peptide more frequently (91%) and never of the 80 kD peptide as compared with patients with normal GFR (33 kD [42%] 80 kD [87%]). The pattern of urinary GBM-related peptides was not specific for the underlying renal disease as in Alport's syndrome.
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PMID:Urinary excretion of glomerular basement membrane-related peptides in children with renal disorders. 315 13

Components were solubilized from human glomerular basement membrane by digestion with collagenase and pepsin or by extraction with guanidine-HCl either directly or after previous digestion with the enzyme. The diverse preparations were used as antigens in the enzyme-linked immunosorbent assay (ELISA) of antibody titers in sera from patients with Goodpasture syndrome and patients with other forms of glomerulonephritis, that is, systemic lupus erythematosus, periarteritis nodosa, and IgA-related nephropathy. Patients with Goodpasture syndrome had high titers of IgG antibodies reacting most strongly with collagenase digests. The antigen(s) was only partly solubilized by guanidine-HCl extraction, was destroyed by pepsin digestion as well as reduction, and partly destroyed by trypsin digestion. The antigen(s) is most likely noncollagenous protein. Antibodies from patients with other forms of nephritis were directed primarily against antigens in guanidine-HCl extracts, while the antigen(s) was not solubilized by collagenase digestion. Pepsin digestion destroyed the antigen(s). The antibodies were of a different class, that is, the patients with systemic lupus erythematosus had IgG and IgA as well as IgM antibodies; the patients with periarteritis nodosa had IgM or IgG and IgA antibodies, while the patients with IgA-related nephritis had the highest recorded titers of IgA but also had IgG as well as IgM antibodies. None of the patients had antibodies directed against triple helical collagen. The antibody response in anti-GBM antibody-related nephritis, then, is different both with respect to antigen and antibody class and depends on the underlying disease syndrome.
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PMID:Antiglomerular basement membrane antibody: antibody specificity in different forms of glomerulonephritis. 613 25

Nonobese diabetic (NOD) mice spontaneously develop immune-mediated insulin-dependent diabetes mellitus and nephropathy, providing an opportunity to study the early molecular events in a model of diabetic glomerulosclerosis. The expression of several genes coding for growth factors and extracellular matrix was examined in microdissected glomeruli, by the use of reverse transcription-competitive polymerase chain reaction, in diabetic NOD mice (mean duration of diabetes, 28.5 +/- 7 days) and age-matched nondiabetic NOD mice with normal glucose tolerance. The levels of mRNA coding for transforming growth factor-beta 1, tenascin, and laminin B1 increased 1.9-, 2.0-, and 1.7-fold, respectively, whereas platelet-derived growth factor (PDGF)-B, alpha 1(IV) collagen, 72-kd collagenase, alpha-smooth muscle actin, and beta-actin mRNA remained stable in the diabetic mice. The kidney advanced glycosylation end-products levels increased 2.1-fold in the diabetic mice, and the diabetic glomeruli showed an accumulation of tenascin and laminin but not of type IV collagen by immunofluorescence microscopy. There was no increase in cell number per glomerulus after the onset of diabetes, a finding consistent with stable PDGF-B and alpha-smooth muscle actin mRNA levels. These findings provide evidence that increased glomerular transforming growth factor-beta 1, but not PDGF-B, mRNA is associated with the up-regulation of tenascin and laminin expression after advanced glycosylation endproduct accumulation, early after the onset of diabetes.
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PMID:Overexpression of transforming growth factor-beta 1 mRNA is associated with up-regulation of glomerular tenascin and laminin gene expression in nonobese diabetic mice. 753 9

We examined metalloproteinase (MMP)-1, -2, -3, and -9 mRNA expression by peripheral blood monocytes from 50 patients with immunoglobulin A (IgA) nephropathy, 20 with membranous nephropathy, 10 with minimal-change nephrotic syndrome, five with focal glomerulosclerosis, 30 with non-IgA proliferative glomerulonephritis, and 40 healthy normal controls who were comparable with regard to age and sex. Monocytes from patients with IgA nephropathy expressed a higher level of MMP-9 mRNA than those from patients with other forms of glomerulonephritis or from healthy controls (MMP-9 to glyceraldehyde-3-phosphate dehydrogenase ratio: IgA nephropathy, 1.68 +/- 0.24; membranous nephropathy, 0.22 +/- 0.08; minimal-change nephrotic syndrome, 0.24 +/- 0.06; focal glomerulosclerosis, 0.32 +/- 0.08; non-IgA proliferative glomerulonephritis, 0.30 +/- 0.12; and healthy controls, 0.16 +/- 0.04). When the biopsy specimens were classified into four grades according to the severity of glomerular and interstitial pathology, highly significant differences were observed among MMP-9 mRNA levels in monocytes from all four groups of patients with IgA nephropathy (grade I, 0.44 +/- 0.09; grade II, 1.06 +/- 0.26; grade III, 2.22 +/- 0.68; grade IV, 2.86 +/- 0.88). In addition, MMP-9 mRNA levels from patients with IgA nephropathy correlated with urinary protein excretion (P < 0.001). However, we detected minimal mRNA expression of MMP-1, -2, and -3 by peripheral blood monocytes from patients with IgA nephropathy or other forms of glomerulonephritis and from normal healthy controls. Our results suggest that increased MMP-9 mRNA expression in circulating monocytes may contribute to the progression of IgA nephropathy.
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PMID:Increased mRNA expression of metalloproteinase-9 in peripheral blood monocytes from patients with immunoglobulin A nephropathy. 871 19


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