Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human gelatinase B was produced from peripheral blood neutrophils and purified by affinity chromatography on gelatin sepharose. This material was used as an antigen to prepare mouse monoclonal antibodies (mAb). The resulting hybridomas were selected on the basis of binding to biotinylated antigen and by a sandwich ELISA using gelatinase-B-specific polyclonal rabbit antiserum and pure natural antigen. Five of these mAb were selected for further characterization. They all displayed variable epitope specificity, binding capacity and inhibitory activity. Whereas mAb REGA-2D9 and REGA-3G12 showed the strongest binding to biotinylated gelatinase B and natural gelatinase B, respectively, mAb REGA-2F9 did not bind biotinylated antigen. None of the mAb displayed cross-reactivity to gelatinase A in a direct ELISA. The mAb REGA-1G8 was found to cross-react with human serum albumin. The binding capacity of the other four mAb with leukocyte gelatinase B was compared and a sensitive sandwich ELISA was developed with the antibodies REGA-3G12 and REGA-2D9 (detection limit 0.5 ng/ml). The mAb REGA-3G12 was unique in that it inhibited catalysis by gelatinase B. This was shown by assaying the degradation of nasal septum type II gelatin in the presence and absence of each of the five mAb. Furthermore, mAb REGA-3G12 inhibited the degradation of biotinylated gelatin in a microtiterplate solution assay. In addition to the potential use of the inhibitory mAb REGA-3G12 in the treatment of diseases with excessive gelatinase B production, several of the described mAb are useful as diagnostic probes to detect gelatinase B in body fluids and tissue samples of patients with multiple sclerosis, rheumatoid arthritis and cancer.
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PMID:Monoclonal antibodies specific for natural human neutrophil gelatinase B used for affinity purification, quantitation by two-site ELISA and inhibition of enzymatic activity. 857 32

Rats were subjected to acute lung injury by the intra-alveolar formation of IgG immune complexes of bovine serum albumin (BSA) and anti-BSA. In this model of injury, complement activation occurs and large numbers of neutrophils invade the interstitium and alveolar space. In the present study, animals were treated with intratracheal catalase concomitantly with anti-BSA or after a lag period of 5-120 min. Catalase treatment at time-zero or at 5 min post injury failed to prevent lung injury as indicated by permeability change, histological features, and neutrophil influx. However, treatment after a delay of 15-30 min (but not 120 min) afforded substantial protection. Consistent with past findings [19], lung injury was accompanied by an accumulation of matrix metalloproteinase 9 (MMP-9) in bronchoalveolar lavage (BAL) fluid. There was a strong correlation between inhibition of injury and reduction in MMP-9 levels. In vitro studies conducted in parallel revealed that unstimulated alveolar macrophages did not produce measurable MMP-9, while there was a large induction following exposure to the same immune complexes that initiated injury in vivo. MMP-2 was also slightly upregulated under the same conditions. Concomitant treatment with catalase greatly inhibited MMP-9 production by macrophages in response to immune complexes, but this treatment had little effect on basal production of either MMP-9 or MMP-2 by macrophage. The same concentration of catalase that suppressed MMP-9 elaboration also inhibited the production of tumor necrosis factor alpha. In contrast, when neutrophils were treated with catalase and then exposed to immune complexes, the antioxidant failed to prevent the release of either MMP-2 or MMP-9. Taken together, these findings demonstrate that antioxidant treatment interferes with elaboration of MMPs by alveolar macrophages. Protection against lung injury is correlated with reduction in MMP levels in the BAL fluid.
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PMID:Time-dependent inhibition of immune complex-induced lung injury by catalase: relationship to alterations in macrophage and neutrophil matrix metalloproteinase elaboration. 1096

Human peripheral blood mononuclear cells (PBMC) upon transendothelial migration interact with subendothelial matrix components and differentiate into macrophages. In order to study whether the shape of the cells as dictated by the extracellular matrix can influence monocyte-macrophage (mo-m(phi)) differentiation, human PBMC were maintained in vitro on a three dimensional collagen I (COL I) lattice and studied for various macrophage specific functions, viz. endocytosis of [(125)I]acetyl bovine serum albumin (BSA), expression of specific cell surface antigens and expression of matrix metalloproteinases (MMPs). The cells maintained in three dimensional COL gel exhibited a higher rate of endocytosis of [(125)I]acetyl BSA than those on COL-coated plastic. FACS analysis showed that the mean fluorescence intensity (MFI) corresponding to monocyte specific LPS receptor CD14 was significantly decreased while MFI corresponding to macrophage specific transferrin receptor CD71 was significantly increased in cells maintained in vitro on three dimensional COL gel compared to two dimensional COL substrata. Expression of macrophage specific MMPs (gelatinase A and gelatinase B) was significantly high in cells maintained on COL gel than on COL I-coated plastic. Appearance of 67 kDa gelatinase in the COL gel suggested that induction as well as activation of MMPs occur when cells are maintained in a three dimensional environment. These results indicate that monocytes undergo a rapid rate of differentiation when maintained in vitro on three dimensional COL I lattice suggesting that apart from the chemical nature of the matrix, the shape of the cells as provided by the matrix also influences mo-m(phi) differentiation.
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PMID:Monocyte-macrophage differentiation in three dimensional collagen lattice. 1147 94

An endotoxin-induced mastitis model was used to study permeability changes associated with increased milk matrix metalloproteinase (MMP) activity in early inflammation. One quarter of two cows was inoculated with endotoxin (Escherichia coli 055:B5). Blood, milk, and whey were collected before and repeatedly after inoculation for 48 h. The profile and amounts of gelatinolytic MMPs were determined by zymography; gelatinase A (72 kD MMP-2) and gelatinase B (92 kD MMP-9) were identified by Western immunoblotting. Bovine serum albumin (BSA) and trypsin inhibitor capacity (TIC) were used as markers of capillary permeability with parallel examination of neutrophil penetration from blood to milk. Five clinical E. coli mastitis milk samples and five milk samples from cows with healthy udders were analyzed to detect whether increased levels of gelatinolytic MMP-2 and MMP-9 have a role in naturally occurring mastitis with endotoxin involvement. Milk MMP levels increased 2h after the endotoxin challenge. Both MMP-2 and MMP-9 were involved in this early proteolytic event. These increased MMP levels are associated with increased capillary permeability, evidenced first by the penetration of small molecular weight proteins, such as BSA and TIC. Later, 6-12h post endotoxin inoculation, neutrophilic leucocytes also entered the site, as they require larger tissue damage in basal membrane and interstitial tissue structures than BSA and TIC to extravasate. In naturally occurring disease, increased MMP-2 and MMP-9 levels were detected in milk. Thus, gelatinases, especially MMP-2, are involved in the early degradation of the blood-milk barrier, which precedes the penetration of blood-derived cellular components into milk in endotoxin-induced mastitis. In the future, measuring MMP in milk/whey might be a useful tool for diagnosing early mastitis.
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PMID:Increase in milk metalloproteinase activity and vascular permeability in bovine endotoxin-induced and naturally occurring Escherichia coli mastitis. 1194 15

Amphoterin is 1 ligand of the receptor for advanced glycation end products (RAGE). We studied expression of amphoterin and RAGE mRNA and proteins in colorectal carcinoma cells and investigated their associations with the invasive activities of cells exposed to advanced glycation end products (AGE). Expression of RAGE and amphoterin was examined in 4 colorectal carcinoma cell lines. All cell lines expressed both RAGE and amphoterin. The effects of RAGE and amphoterin on cell growth (MTT assay), migration (wound healing assay) and invasion (in vitro invasion assay) were tested by treatment of cells with RAGE and amphoterin antisense S-oligodeoxynucleotides (ODNs). Cell growth, migration and invasion were inhibited significantly in Colo320 and WiDr carcinoma cells treated with RAGE and amphoterin antisense S-ODNs compared with sense-treated cells. Differences in ligand activity between amphoterin and AGE were examined with AGE-bovine serum albumin (BSA). AGE-BSA decreased cell growth, migration and invasion of amphoterin antisense S-ODN-treated Colo320 and WiDr cells compared with those of cells treated with Colo320 conditioned medium. Phosphorylation of extracellular signal-regulated kinase-1/2, Rac1 and AKT and production of matrix metalloproteinase 9 were increased to a greater degree by amphoterin than by AGE-BSA. In contrast, production of inducible nitric oxide synthase and nuclear factor-kappaBp65 were increased to a greater degree by AGE-BSA than by amphoterin.
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PMID:Differential effects between amphoterin and advanced glycation end products on colon cancer cells. 1264 Jun 79

Poly-[N-(2-hydroxyethyl)-L-glutamine] (PHEG) and poly(ethylene glycol) (PEG)-grafted PHEG conjugates of N,N-di(2-chloroethyl)-4-phenylenediamine mustard (PDM) were synthetised. A collagenase-sensitive oligopeptide spacer was selected to link the cytotoxic agent PDM onto the polymeric carrier. First, the oligopeptide-drug conjugate, L-pro-L-leu-gly-L-pro-gly-PDM, was prepared. In a second step, the low molecular weight PDM derivative and PEG-NH(2) were coupled to a N,N-disuccinimidylcarbonate activated PHEG. Dynamic laser light scattering measurements indicated the formation of aggregates. The presence of human serum albumin had no significant effect on the diameter of the conjugates. The hydrolytic stability of the conjugates was investigated in buffer solutions. The conjugates showed an improved stability compared to the parent nitrogen mustard. The enzymatic degradation studies of the polymeric conjugates were performed in the presence of collagenase type IV (Clostridiopeptidase A; EC 3.4.24.3), cathepsin B (EC 3.4.22.1), cathepsin D (EC 3.4.23.5) and tritosomes. Only the bacterial collagenase type IV was able to cleave the spacer releasing free PDM and its peptidyl derivative, gly-L-pro-gly-PDM. The in vitro cytotoxicity of the conjugates was evaluated against HT1080 fibrosarcoma cells and MDA adenocarcinoma cells. All conjugates showed low toxicity towards these cell lines.
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PMID:Synthesis and in vitro evaluation of macromolecular antitumour derivatives based on phenylenediamine mustard. 1566 87

The biomarkers associated with coronary artery lesions (CAL) secondary to Kawasaki disease (KD) in Chinese children were investigated by using Meta-analysis. We searched documents published from January 1997 to December 2009 from medical electronic databases. According to inclusion and exclusion criteria, eligible full-text papers were identified. We conducted a comprehensive quantitative analysis by using Stata10.0 statistical software package to assess the heterogeneity among the documents, calculated the summary effect and analyze publication bias and sensitivity. A total of 92 documents and 16 biomarkers were identified. All documents were case-control studies, and included 2398 patients in CAL group and 5932 patients in non-CAL (NCAL) group. The Meta-analysis showed that the levels of platelet count, platelet hematocrit (PCT), neutrophils count, platelet distribution width (PDW), mean platelet volume (MPV), erythrocyte sedimentation rate (ESR), cardiac troponin I (cTnI), and endothelin-1 (ET-1) in CAL group were significantly higher than those in NCAL group, and serum albumin (Alb) and hemoglobin (Hb) levels were significantly lower in CAL group (all P<0.05). White blood cell (WBC) count, serum sodium, matrix metalloproteinase 9 (MMP-9), total cholesterol (TC), hematocrit (HCT) and CD3+T lymphocytes percentage had no statistically significant difference between the two groups. In conclusion, our results indicated that the 10 biomarkers including platelet count, neutrophils count, PCT, PDW, MPV, ESR, cTnI, ET-1, Alb and Hb were associated with CAL, and may be involved in the pathogenesis of CAL. The biomarkers of WBC count, serum sodium, MMP-9, TC, HCT, and CD3+T lymphocytes percentage bore no relationship with the development of CAL among Chinese children with KD.
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PMID:A meta-analysis of the biomarkers associated with coronary artery lesions secondary to Kawasaki disease in Chinese children. 2203 66

Use of the common marmoset (Callithrix jacchus) as a non-human primate experimental animal has increased in recent years. Although wasting marmoset syndrome (WMS) is one of the biggest problems in captive marmoset colonies, the molecular mechanisms, biochemical markers for accurate diagnosis and a reliable treatment remain unknown. In this study, as a first step to finding biochemical marker(s) for the accurate diagnosis of WMS, we conducted blood cell counts, including hematocrit, hemoglobin and platelets, and examined serum chemistry values, including albumin, calcium and levels of serum matrix metalloproteinase 9 (MMP9), using a colony of marmosets with and without weight loss. MMP9 is thought to be an enzyme responsible for the degradation of extracellular matrix components and participates in the pathogenesis of inflammatory conditions, such as human and murine inflammatory bowel disease, which, like WMS, are characterized histologically by inflammatory cell infiltrations in the intestines. The values of hematocrit and hemoglobin and levels of serum albumin and calcium in the WMS group were significantly decreased versus the control group. The platelet values and serum MMP9 concentrations were increased significantly in the WMS group compared with the control group. MMP9 could be a new and useful marker for the diagnosis of WMS in addition to hematocrit, hemoglobin, serum albumin and calcium. Our results also indicate that MMP9 could be a useful molecular candidate for treatment.
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PMID:Serum matrix metalloproteinase 9 (MMP9) as a biochemical marker for wasting marmoset syndrome. 2687 41

Wasting marmoset syndrome (WMS) has high incidence and mortality rates and is one of the most important problems in captive common marmoset (Callithrix jacchus) colonies. Despite several reports on WMS, little information is available regarding its reliable treatment. We previously reported that marmosets with WMS had high serum levels of matrix metalloproteinase 9 (MMP9). MMP9 is thought to be a key enzyme in the pathogenesis of inflammatory bowel disease, the main disease state of WMS, and is activated by plasmin, a fibrinolytic factor. In a previous study, treating mice with an antibody to inhibit plasmin prevented the progression of inflammatory bowel disease. Here we examined the efficacy of tranexamic acid, a commonly used plasmin inhibitor, for the treatment of WMS, with supportive measures including amino acid and iron formulations. Six colony marmosets with WMS received tranexamic acid therapy with supportive measures for 8 wk. The body weight, Hct, and serum albumin levels of these 6 marmosets were increased and serum MMP9 levels decreased after this regimen. Therefore, tranexamic acid therapy may be a new and useful treatment for WMS.
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PMID:Tranexamic Acid and Supportive Measures to Treat Wasting Marmoset Syndrome. 2830 50