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 neutral proteinase secreted by rabbit synovial fibroblasts in parallel with specific collagenase was partially purified by ion-exchange chromatography. At pH 7.6 this proteinase degraded 35S-labelled bovine nasal proteoglycan and azo-casein. The enzymic activity was inhibited by EDTA, 1,10-phenanthroline and serum, whereas di-isopropyl phosphorofluoridate and soya-bean trypsin inhibitor had little effect. By gel filtration the apparent mol.wt. of the enzyme was 25000. The fibroblast neutral proteinase was compared with the proteoglycan-degrading neutral proteinases of rabbit polymorphonuclear-leucocyte granules. Two distinct activities were found in the granules: one was inhibited by soya-bean trypsin inhibitor and the other by EDTA. The proteoglycan-degrading proteinases of rabbit fibroblasts and polymorphonuclear leucocytes at acid pH also were examined. Both cathepsin D and a thiol-dependent proteinase contributed to the degradation of proteoglycan at pH 4.5.
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PMID:Proteoglycan-degrading enzymes of rabbit fibroblasts and granulocytes. 3 Apr 51

1. Enzymes that may contribute to liquefaction of the cornea in retinol-deficient animals and in man have been studied using rat cornea. The established technique of culturing tissue fragments and determining the activity of collagenase (EC 3-4-24-3) and other enzymes in the medium after different periods of culture was used. 2. A collagenolytic system was detected in the media from cultures of rat corneas. This system probably consists of at least two enzymes, a collagenase and a neutral proteinase. 3. Both proteolytic and specific collagenolytic activity were greater in media from retinol-deficient rat corneas. The hydroxyproline level increased in parallel with the increase in enzyme activity. 4. In the final stages of retinol deficiency the cornea is invaded by granulocytes and other cells of the blood and we suggest that destruction of cornea collagen may be due largely to the activity of the enzymes from these cells.
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PMID:Collagenase and other proteinases in the cornea of the retinol-deficient rat. 16 77

We have studied the effect of colchicine and related compounds on secretion of enzymes by thioglycollated-elicited mouse peritoneal macrophages in culture. Colchicine stimulated secretion of inducible neutral proteinase activities of elastase (EC 3.4.21.11), collagenase (EC 3.4.24.3), gelatinase (pepsin B; EC 3.4.23.2), and azocaseinase 2- to 6-fold for a period of several days, but inhibited the production and release of lysozyme (mucopeptide N-acetylmuramoylhydrolase; EC 3.2.1.17), a noninducible macrophage secretory product. Parallel changes were observed in cell morphology and secretion after treatment with colchicine, Colcemid, and vinblastine, but not with lumicolchicine, and these effects could be gradually reversed by withdrawal of colchicine. Cytochalasin B also stimulated secretion of elastase 2- to 3-fold but did not influence release of lysozyme. These results demonstrate that tubulin-binding drugs may have opposite effects in macrophages than those usually reported for other experimental systems and also provide evidence for the nonparallel discharge of different macrophage secretion products.
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PMID:Secretion of macrophage neutral proteinase is enhanced by colchicine. 17 59

Polymorphonuclear (PMN) leukocytes mediate that phase of inflammation at which vascular responses become translated into tissue injury. After phagocytosis, the PMN leukocyte generates derivatives of molecular oxygen (O2-.,OH., and H2O2) that stimulate a metabolic burst and assist in the killing of microorganisms. They also release oxidation products of membrane fatty acids (e.g., arachidonate), which are detected as thromboxanes and protaglandins. After interaction of phagocytic ligands (immune complexes and C3b-opsonized particles), the PMN leukocyte secretes lysosomal enzymes from open phagocytic vacuoles, and, especially when phagocytosis is blocked by cytochalasin B, secretes them directly into the cell's surrounding fluids. Secretion is enhanced by agents that elevate intracellular levels of cyclic GMP, and inhibited by agents that raise cyclic AMP. These reciprocal changes are associated with assembly and disassembly (respectively) of cytoplasmic microtubules. These cytoskeletal structures, together with contractile elements, regulate in part the secretory events of inflammation in which lysosomal constituents (e.g., elastase, collagenase, and cathepsin G) are diverted from their intracellular depots to an inappropriate assault on the tissues of the host.
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PMID:Polymorphonuclear leukocytes as secretory organs of inflammation. 21 Feb 34

Chemical and enzymatic properties of four collagenases newly isolated from anaerobic Clostridium histolyticum, aerobic Achromobacter iophagus, and from two lower eucaryotes, the fungus Entomophthora coronata and the insect Hypoderma lineatum are reviewed. The problems of their biosynthesis and precursors, namely the effect of induction of collagenase and neutral proteinase in Achromobacter by their macromolecular substrates are discussed. The two bacterial collagenases are Zn-metallo-enzymes; the highly purified Clostridium collagenase contains cyst(e)ine, serine phosphate and tryptophan additionally to amino acids reported previously. Achromobacter collagenase has the highest specific activity of all collagenases; it yields by autolysis enzymatically active degraded forms. The active dimer is composed of two identical subunits of molecular weight 35,000. Similarities between Achromobacter collagenase, thermolysin and Bacillus subtilis neutral proteinase in molecular weight, amino acid composition, and amino acids important for the active sites are discussed. The two collagenases from low eucaryotes are serine proteinases; Hypoderma collagenase is homologous to the trypsin family in the amino terminal sequence. The initial cleavage of native collagen by highly purified bacterial collagenases occurs in the central helical part of the alpha chains and not progressively from the amino terminal end. One of the two initial cleavages produced by Achromobacter collagenase is situated in the region cleaved specifically by vertebrate collagenases, but with different bond specificity. The same is true for the insect collagenase. Entomophthora collagenase is a proteinase of broad specificity which also cleaves collagen in its helical parts. All four collagenases also degrade other proteins according to their bond specificity.
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PMID:Some newly characterized collagenases from procaryotes and lower eucaryotes. 22 May 20

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

Rabbit bone-marrow macrophages and fibroblasts were cultured, independently or together, with pieces of 35S-labelled cartilage or at the surface of dried [14C]collagen gels. Each type of cell, cultivated alone, rapidly degraded the proteoglycan of cartilage, but only the fibroblasts degraded collagen. The co-culture of both types of cell had no consistent effect on the rate of proteoglycan degradation, but it stimulated the rate of collagen degradation. In parallel, the accumulation of collagenase in the culture fluid was enhanced but not that of neutral proteinase. Coinditioned media from macrophage cultures added to cultures of fibroblasts had the same effect as the living macrophages in stimulating the production of collagenase. Their action was itself enhanced when the macrophages had been activated by concanavalin A-stimulated spleen-cell factors. These data suggest that fibroblasts may act as effector cells in producing collagenase and degrading collagen in response to soluble factors released by macrophages under the control of lymphocyte factors.
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PMID:Macrophage-fibroblast interactions in collagenase production and cartilage degradation. 23 75

Polymorphonuclear leukocytes (PMNs) are one of the main sources of enzymes responsible for tissue damage in inflammatory processes. These enzymes are stored in two types of cytoplasmic granules. Azurophil granules contain lysosomal hydrolases, neutral serine proteinases, and bactericidal elements (myeloperoxidase and lysozyme). Specific granules contain collagenase, lysozyme and lactoferrin but lack lysosomal hydrolases. PMNs store all four classes of tissue proteinases, carboxyl, thiol and serine proteinases in the azurophil granules, and metallo proteinases in the specific granules. Three serine proteinases have been identified, elastase, cathepsin G and a third enzyme, which together account for a large proportion of the protein of the azurophil granules. In the course of phagocytic events, all these enzymes are released extracellularly. The neutral proteinases degrade proteoglycans and collagen. In vitro, they stimulate B-lymphocytes, which suggests that they may have immuno-potentiating activity when they are released at sites of chronic inflammation.
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PMID:The polymorphonuclear leukocyte. 34 82

Neutrophils and macrophages produce, store and release large amounts of various acid and neutral proteinases. The two main proteinases of neutrophils are elastase and cathepsin G. They are localized in the azurophil granules, together with proteinase 3 and the acid cathepsins B and D. In addition neutrophils contain collagenase in the specific granules, acid proteinases in the C-particles and plasminogen activator in organelles with the characteristics of secretory vesicles. The granule-bound proteinases are released during phagocytosis while plasminogen activator is apparently secreted. In macrophages, the acid hydrolases are bound to lysosomes while the neutral proteinases are confined to secretory vesicles. The main mechanism of enzyme release in macrophages is secretion. Lysosomal hydrolases are also released by phagocytosis. Enzyme secretion is a characteristic property of activated or inflammatory macrophages. Macrophages become activated after phagocytosis of certain particles and the metabolic burst appears to be an initial event in the activation process. The action of neutrophils and of purified elastase or plasmin on cartilage was tested. These experiments indicate that neutrophil-mediated degradation of cartilage proteoglycans is largely dependent on elastase.
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PMID:Cellular mechanisms of proteinase release from inflammatory cells and the degradation of extracellular proteins. 39 84

A possible mechanism for tumor cell invasion of normal tissue might be secretion of proteolytic enzymes. This study compares and contrasts production and secretion of proteinases by cell cultures of normal and chemically transformed mouse epithelial cells. Lysates of normal and neoplastic cells contain similar amounts of neutral proteinase, cathepsin D and plasminogen activator. Neither collagenase nor elastase could be identified in lysates of, or serum-free culture medium bathing, normal or neoplastic cells. Neoplastic cells secrete ten times more plasminogen activator than normal cells. Our data support the hypothesis that plasminogen activator produced by neoplastic cells could fuction to activate latent proteolytic enzymes secreted by connective tissue cells which might result in spread of neoplastic cells into normal tissue.
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PMID:Production and secretion of proteolytic enzymes by normal and neoplastic cells. 45 22


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