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)

Purified human granulocyte collagenase was inactivated by serum through the formation of complexes with alpha 1-antitrypsin and alpha 2-macroglobulin. A molar combining ratio of 1:1 was observed for each inhibitor. The affinity of alpha 2-macroglobulin was about 10 times that of alpha 1-antitrypsin for granulocyte collagenase. The molar concentration of alpha 1-antitrypsin in the blood exceeds that of alpha 2-macroglobulin by about 12 times, so that the inhibitors may be equally important for defence against granulocyte collagenase.
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PMID:Neutral proteases of human granulocytes. IV. Interaction between human granulocyte collagenase and plasma protease inhibitors. 6 76

A number of soluble proteins contained in human aortic intimal tissue was extracted into buffered saline (pH 7.4) and identified and quantitated by immunoelectrophoresis and immunodiffusion. The proteins included IgA, IgG, IgM, B1C (C3), alpha 1-antitrypsin, alpha 2-macroglobulin, fibrinogen, albumin, LDL, HDL, alpha 1-acid glycoprotein, beta 2-glycoprotein, transferrin and ceruloplasmin. The concentration of soluble proteins was significantly higher in the atherosclerotic intima than in the normal intima. The diseased intima also contained a small amount of tissue-bound IgG, IgA and B1C which was extractable with citrate buffer at pH 3.2. The vascular band IgG, and B1C were shown by enzymatic and immunohistochemical studies to be closely associated with the collagenous tissue of the plaque. The Ig contained in the atherosclerotic plaque may be derived in part from the biosynthesis of Ig by the artery, since the incorporation of 14C-labeled leucine into IgG by the atheromatous plaque was demonstrable by radioimmunoelectrophoresis. In contrast to the diseased artery, the normal artery did not synthesize IgG and did not contain vascular bound IgG or complement. However, the normal artery was capable of fixing IgG and B1C eluted from the diseased artery. The present studies suggested that the IgG contained and synthesized by the plaque might represent an immune response to an endogenous or exogenous antigen closely associated with plaque collagen. IgG and B1C either alone or in the form of an immune complex also may play an important role in phagocytosis in the plaque and thereby influence the course of atherosclerosis. The proteolytic inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin, found in relatively high concentrations in the plaque, could enhance fibrosis of the lesion because of thier known inhibitory effects on collagenase and elastase.
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PMID:Soluble proteins in the human atherosclerotic plaque. With spectral reference to immunoglobulins, C3-complement component, alpha 1-antitrypsin and alpha 2-macroglobulin. 9 93

Peritoneal fluids from patients with diffuse peritonitis secondary to perforation of the appendix contained large quantities of collagenase and elastase. The enzymes, which existed in the form of complexes with plasma protease inhibitors, probably had been released from the granulocytes. The two enzymes had linked almost half of the alpha 1-antitrypsin and four fifths of the alpha 2-macroglobulin in the fluid. Evidence that regional defense against protease had failed was obtained by finding the C3 component of complement completely converted. Toxic peptides probably had been released. Recognition of plasma protease inhibitors as an important part of the regional defense against protease also suggested use for therapy. We lavaged the peritoneum postoperatively with fluid that did not contain plasma inhibitors but with volumes large enough to eliminate the accumulation of enzymes for the granulocyte.
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PMID:Collagenase and elastase released during peritonitis are complexed by plasma protease inhibitors. 17 59

The synovial fluid (SF) of RA patients contains large amounts of PMN which are well equipped with neutral enzymes to degrade articular cartilage: elastase and cathepsin G, which both destroy proteoglycans and native collagen, as well as 2 types of collagenoases. Indirect evidence suggests that PMN might be important in the destruction of RA articular cartilage. In 19 SF of RA patients no free elastase or collagenase was found. Using immune histochemical methods, we observed that PMN and macrophages of SF contain both elastase and alpha 1-anti-trypsin and alpha 2-macroglobulin. Peripheral PMN - but not monocytes - contain elastase, however both types of cells lack alpha 1-antitrypsin and alpha 2-macroglobulin. Elastase is demonstratable in the superficial layer of pannus free RA articular cartilage. These findings suggest that neutral proteinases from PMN in RA SF are generally neutralized by physiologic inhibitors and removed by phagocytes. The enzyme-inhibitor interaction might be bypassed during "frustrated phagocytosis" so that enzymes like PMN elastase can damage RA articular cartilage.
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PMID:[Chronic polyarthritis: role of polymorphonuclear leukocytes in the destruction of pannus-free articular cartilage]. 23 68

To our knowledge, necrotizing lid tumors occurring in the context of a necrotizing lobular panniculitis have not yet been described in the literature. Our patient, a 75-year-old male, presented with indolent, nonmoveable subcutaneous lumps that were centrally ulcerating. They appeared first on his upper lid, then on his lower lid and thereafter on the neck, back, upper extremity and abdomen, especially in the area of his cholecystectomy scar. A thorough work-up, which included repeated histopathological examinations performed by several laboratories, led to the diagnosis of an idiopathic necrotizing lobular panniculitis. A serum level determination performed later revealed no alpha 1-antitrypsin deficiency. As the eye-lid's subcutaneous tissue lacks fat, the association between the necrotizing lid tumors and the necrotizing panniculitis appears to be a paradox. In spite of the normal alpha 1-antitrypsin serum levels--determined when the patient's lesions had long ago healed--we think in retrospect that the differential diagnosis should have included the possibility of a decreased alpha 1-antitrypsin serum level (e.g. heterozygous MZ-phenotype). An alpha 1-antitrypsin level deficiency--with resulting decreased inhibition of collagenase and elastase--could account for the necrotizing process that also occurred in the eyelid's subcutaneous tissue. In the Van Gieson stain of this patient's eyelid biopsy, fragmentation of all visible collagen and elastic fibers was noted. In our opinion, the differential diagnosis does include lid involvement with secondary panniculitis caused by partially decreased alpha 1-antitrypsin serum levels and--by exclusion--idiopathic necrotizing lobular panniculitis. Therapeutic possibilities are briefly discussed.
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PMID:[Recurrent eyelid tumor in necrotizing panniculitis]. 161 47

Three patients (a 71-year-old man and 2 women, 73 and 50 years, respectively) with recurrent panniculitis associated with alpha 1-antitrypsin deficiency are presented. Because the concept of chronic and exaggerated inflammatory response in the patients with alpha 1-antitrypsin deficiency is based on the theory of protease-antiprotease imbalance, we suggest that tetracyclines will alleviate this condition. Indeed, tetracyclines were found to inhibit collagenase activity. The total remission of the condition in these 3 patients underlines for the first time the effects of doxycycline on a condition characterized by deficiency of the antiprotease system. A review of the 23 reported cases of panniculitis associated with alpha 1-antitrypsin deficiency is presented in table form.
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PMID:Use of anti-collagenase properties of doxycycline in treatment of alpha 1-antitrypsin deficiency panniculitis. 167 18

High yields of human hepatocytes (up to 23 X 10(6) viable cells/g) were obtained from small surgical liver biopsies (1 to 3 g) by a two-step collagenase microperfusion method. Cell viability was about 95%, attachment efficiency of hepatocytes seeded on fibronectin-coated plates was 80% within 1 h after plating, and cells survived for about 2 wk in serum-free Ham's F12 containing 0.2% bovine serum albumin, 10(-8) M insulin, and 10(-8) M dexamethasone. To evaluate the metabolism of human hepatocytes in serum-free conditions, we measured their most characteristic biochemical functions and compared them to those reported for human liver. After 24 h in culture, glycogen content was 1250 +/- 177 nmol glucose/mg cell protein and remained stable for several days. Gluconeogenesis from lactate in hormone-free media was (3.50 +/- 0.17 nmol glucose.mg-1.min-1) similar to that reported for human liver. Insulin at 10(-8) M activated glycolysis (X1.40) and glycogenesis (X1.34), and glucagon at 10(-9) M stimulated gluconeogenesis (X1.35) and glycogenolysis (X2.18). Human hepatocytes synthesized albumin, transferrin, fibrinogen, alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, haptoglobin, alpha 2-macroglobulin, and plasma fibronectin and excreted them to the culture medium. Maximum protein synthesis was stimulated by 10(-9) M dexamethasone. Basal urea synthesis oscillated between 2.5 and 3.5 nmol.mg-1 cell protein.min-1, about 5 times the value estimated for human liver. Cytochrome P-450 decreased in culture but it was still 20% of freshly isolated hepatocytes by Day 5 in culture. In addition, ethoxycumarin-O-deethylase and aryl hydrocarbon hydroxylase could be induced in vitro by treatment with methyl cholanthrene. Glutathione levels were similar to those reported for human liver (35 nmol.mg-1). The results of our work show that adult human hepatocytes obtained from small surgical biopsies and cultured in chemically defined conditions express their most important metabolic functions to an extent that is similar to that reported for adult human liver.
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PMID:Culture of human hepatocytes from small surgical liver biopsies. Biochemical characterization and comparison with in vivo. 215 94

Highly purified human polymorphonuclear leucocyte collagenase cleaved human alpha-1-proteinase inhibitor (alpha 1-PI) at the carboxyl site of Phe352 (P7). The inhibitor was thereby rapidly inactivated and generated a primary degradation product as shown by reverse-phase HPLC and N-terminal sequencing. Prolonged incubation of the modified inhibitor with polymorphonuclear leucocyte collagenase led to the generation of a secondary degradation product with additional cleavage at the carboxyl site of Pro357 (P2).
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PMID:Inactivation of human plasma alpha 1-proteinase inhibitor by human PMN leucocyte collagenase. 215 25

Inactivation of the plasma serine-proteinase inhibitor alpha 1-antitrypsin (alpha 1-AT) by neutrophil metalloproteinases has been reported [Vissers, George, Bathurst, Brennan & Winterbourn (1987) Fed. Proc. Fed. Am. Soc. Exp. Biol. 46, 1390a; (1988) J. Clin. Invest. 82, 706-711; Desrochers & Weiss (1988) J. Clin. Invest. 81, 1646-1650]. To identify the enzyme responsible, supernatant from neutrophils stimulated with phorbol 12-myristate 13-acetate was subjected to preparative SDS/PAGE, both with and without activation of latent metalloproteinases with HgCl2. The lanes were subsequently sliced into pieces, the slices incubated with equimolar amounts of type I collagen and alpha 1-AT in the presence of HgCl2, and the reaction products separated by SDS/PAGE. With the latent supernatant, the characteristic collagen-cleavage products and cleaved alpha 1-AT were present in the same slices, corresponding to an Mr of 80,000-85,000. On treatment with HgCl2 both degradative activities underwent the same molecular-mass shift to a position corresponding to Mr 60,000-65,000. Western blots of neutrophil supernatants, using a polyclonal antibody to purified collagenase, showed Mr values of 83,000 for the latent enzyme and 63,000 for the HgCl2-activated enzyme. Neutrophil collagenase was purified to homogeneity and shown also to exist in a second latent form with Mr 70,000. When activated to the Mr-63,000 form by HgCl2 and incubated with equimolar amounts of collagen and alpha 1-AT, collagenase cleaved alpha 1-AT at almost twice the rate at which collagen was cleaved. alpha 1-AT cleavage was inhibited by 1,10-phenanthroline and by high concentrations of collagen. That the purified collagenase did not contain a contaminant proteinase such as stromelysin was indicated by inability of the preparation to cleave casein. Taken together these results lead us to conclude that neutrophil collagenase is capable of degrading alpha 1-AT. Neutrophil gelatinase also cleaved alpha 1-AT, but cleavage was slow when compared with its activity against gelatin.
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PMID:Human neutrophil collagenase cleaves alpha 1-antitrypsin. 217 52

Hepatocytes were isolated by application of the two-step collagenase perfusion technique to pieces of human liver. The cells were incubated in serum-free medium or 10% FCS-medium supplemented with insulin, glucagon and dexamethasone, and kept in culture for more than 2 weeks. Seventy-five per cent of the medium was changed regularly and assayed for alpha 2-macroglobulin (alpha 2-M), pregnancy zone protein, alpha 1-antitrypsin and albumin by means of ELISA. Significant amounts of alpha 2-macroglobulin were present in all cultures. During incubation, alpha 2-M accumulated in the medium and the quantity of alpha 2-M released from the cells by far exceeded protein associated with hepatocytes prior to incubation. In 24 h 10(6) hepatocytes secreted 160.5 +/- 82.2 ng of alpha 2-M (mean +/- SD, n = 5). Cell-associated, as well as secreted alpha 2-M appeared to be on native form, as determined by immunoisolates from lysed cells and culture supernatants. Pregnancy zone protein was only detected in about 50% of the cultures and its rate of secretion was less than 2 ng 24 h-1 per 10(6) cells. In contrast, culture medium contained considerable quantities of alpha 1-antitrypsin and albumin. In 24 h, 10(6) hepatocytes released greater than 2 micrograms alpha 1-antitrypsin and greater than 5 micrograms albumin. The present study suggests the hepatocyte to be of major importance for the synthesis of intravascular alpha 2-M.
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PMID:Synthesis and secretion of alpha 2-macroglobulin by human hepatocytes in culture. 246 99


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