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)

Pinocytosis and prostaglandin E2 production are two major functions of the mononuclear phagocyte system. The goal of this study was to compare the pinocytosis of horseradish peroxidase and the prostaglandin E2 production between the hepatic and peritoneal resident macrophages in the mouse. Hepatic resident macrophages were isolated by collagenase digestion, differential centrifugation and adherence. Peritoneal resident macrophages were isolated by peritoneal cavity washing followed by adherence. Horseradish peroxidase was endocytosed by hepatic macrophages at a significantly higher rate (118 +/- 12 ng/10(6) cells/60 min) than by peritoneal macrophages (21 +/- 4 ng/10(6) cells/60 min). Prostaglandin E2 production was measured in the culture medium of unstimulated and lymphokine-stimulated hepatic and peritoneal resident macrophages. Prostaglandin E2 concentration in the culture medium of unstimulated peritoneal macrophages was 36.6 +/- 26.8 ng/ml after a 24 h incubation. It was increased by 83 p. 100 in presence of a lymphokine-enriched secondary mixed lymphocyte culture supernatant. In contrast, hepatic macrophages did not produce any significant amount of prostaglandin E2, even if they were incubated in presence of lymphokines. This study shows that hepatic resident macrophages have a higher pinocytic capacity than peritoneal resident macrophages, suggesting that the role of the liver in the clearance of gut-derived antigens is not only due to its portal irrigation but also to the presence of macrophages highly differentiated in their endocytotic properties. The lack of prostaglandin E2 production in hepatic macrophages, in basal conditions as well as after lymphokine-stimulation, suggests that these cells play a minor role in the regulation of the immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparative study of pinocytosis and the production of prostaglandin E2 by hepatic and peritoneal resident macrophages in mice]. 386 Apr 55

In vitro studies were carried out on isolated rat hepatocytes to examine further the proposed cytoprotective actions of prostaglandins (PG) using carbon tetrachloride (CCl4) as the toxic agent. Isolated hepatocytes, prepared by collagenase, were cultured in Leibowitz-15 medium. Following preincubation, CCl4 (300 or 150 micrograms/ml) was added to the hepatocytes. Treatment with Indomethacin (INDO), 16, 16-dimethyl-PGE2(PGE2) and prostacyclin (PGI2) was assayed in the cultures. Cell damage was measured by lactic dehydrogenase (LDH) release. 6-keto-PGF1 alpha was measured in the supernatant by direct radioimmunoassay. The results showed PGI2 (30.0 ng/ml) treatment 30 min after CCl4 (300 micrograms/ml) addition to be highly protective (p less than 0.001 versus CCl4 control). PGE2 (3 ng/ml) showed similar protection (p less than 0.001). INDO (2 micrograms/ml) following CCl4 (150 micrograms/ml) demonstrated increased cell death (p less than 0.001). INDO (0.5 micrograms/ml) reduced 6-keto-PGF1 alpha production (p less than 0.05). Low dose ethanol (1.5 micrograms/ml) increased 6-keto-PGF1 alpha production (p less than 0.05). Ethanol (1.5 micrograms/ml), added to stimulate endogenous PG production, was cytoprotective when added prior to CCl4 (p less than 0.01). This protection was suppressed by INDO. Ethanol added after CCl4 was not protective. We conclude that exogenously added PGI2 and PGE2 are cytoprotective in this in vitro model and that endogenous PG production may play a protective role in the initial stages of cellular damage.
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PMID:Cytoprotective effect of prostaglandins on isolated rat liver cells. 388 50

16,16-Dimethyl PGE2 (dmPGE2) has previously been shown to protect the in vivo rat liver against CCl4-induced damage. These studies were undertaken to determine if this protection could be demonstrated in vitro where factors of absorption, secretion, and blood flow are not present. Primary hepatocyte cultures were established by perfusing rat liver with collagenase. Hepatocytes were plated at a density of 2 X 10(4) cells/cm, allowed 90 min to attach, then stabilized in L15 medium for 18 h. Hepatocytes were then challenged with CCl4 with concomitant exposure to 10(-9) to 10(-5) M dmPGE2, stearic acid, oleic acid, or ethanol vehicle (0.00001 to 0.1%). After 1 h, challenge was aspirated and cells were stained with 0.04% trypan blue to determine viability. Hepatocytes in the vehicle groups took up more trypan when exposed to CCl4 than those treated with dmPGE2, stearic acid, or oleic acid at concentrations of 10(-9) to 10(-7) M. At 0.1% ethanol vehicle protected as well as all other treatments. Protection against CCl4 by dmPGE2, stearic, and oleic acids as well as high concentrations of ethanol may occur by altering the metabolism of CCl4.
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PMID:16,16-Dimethyl PGE2 and fatty acids protect hepatocytes against CCl4-induced damage. 403 Jun 26

Localization of NAD+-dependent (type I) 15-hydroxyprostaglandin dehydrogenase (15PGDH) in the rat kidney was examined using an ultramicro assay of the enzyme activity based on the enzymatic cycling method. The enzyme activities during first 3 weeks of age were 30- to 40-fold higher than the adult and rapidly decreased by 4th week. 15PGDH activities measured with either PGE2 or PGF2 alpha as a substrate were five times higher in slices from midcortical or juxtamedullary layers than in slices from the superficial cortex of 3 week-old rat kidney. Little activity was found in inner medulla and papilla. When the enzyme activity was assayed using isolated nephron segments dissected from collagenase treated slices of 3 week-old rat kidneys, the activity was localized only in the proximal convoluted and straight tubules with either PGs (PGE2: 1.75 +/- 0.25 in PCT, 7.70 +/- 1.19 in PST, and PGF2 alpha: 1.63 +/- 0.39, 6.18 +/- 1.52 pmoles NADH/mm/40 min). The kinetic analysis for renal 15PGDH of 3 week-old rats revealed that Km for PGE2 (8.4 microM) was lower than that for PGF2 alpha (22.6 microM) with constant NAD+, while Vmax for both was similar. In contrast, both Km and Vmax for NAD+ were identical with either PGs. These data suggest that the rate-limiting factor of type I 15PGDH is the concentration of prostaglandins in the kidney rather than the concentration of NAD+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Localization and properties of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase activity in the rat kidney. 403 73

Stimulation of synovial cell prostaglandin production by a factor obtained from casein-induced peritoneal polymorphonuclear (PMN) cells has been investigated. Both the extract and short time cultured medium of rat peritoneal PMN cells stimulate prostaglandin (PG)E2 production as well as collagenase production in the culture of rat synovial cells. PGE2 production by the cells in the presence of the PMN factor is much faster (5 to 24 hr) than collagenase production (24 hr or later, Biomedical Res. 3, 506-516, 1982). This stimulating factor is confirmed to be derived from PMN cells, based on the purification of the cells from peritoneal exudate cells by the Ficoll-Urographin method. Elution profile of the factor on gel filtration has indicated that both PGE2 and collagenase productions by synovial cells are stimulated by the same effluent fractions corresponding to molecular weights of 15,000 - 20,000 daltons and 30,000 - 40,000 daltons. These results suggest that PMN cells are involved in PG production as well as collagenase production in the inflamed tissue by stimulating connective tissue cells such as synovial cells.
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PMID:Stimulation of prostaglandin synthesis in cultured rat synovial cells by a factor derived from polymorphonuclear leukocytes. 608 18

Adherent synovial cells (ASC) were obtained from minced synovium from patients with rheumatoid arthritis by dissociating the lining cells from the extracellular matrix and dispersing them with proteases. These cells produce high levels of latent collagenase in primary culture. With passage of ASC, collagenase levels decrease but can be stimulated by a soluble factor (MCF) released in vitro from cultured human blood monocyte-macrophages. Monocyte cultures exposed to aggregated immunoglobulin, Fc fragments of immunoglobulin or concanavalin A (Con A) increase production of MCF several-fold more than the control cultures. MCF production by monocytes exposed to Fab fragments does not differ from controls. Although aggregated immunoglobulin, Fc fragments, and Con A stimulate PGE2 synthesis and secretion by human monocytes, the effects on MCF production are not mediated by PGE2 since concentrations of indomethacin that completely block PGE2 production do not inhibit MCF production. These findings of increased production of MCF by monocytes in response to substances that probably exert their effects via surface receptors could be relevant in interpreting the in vivo role of immune complexes in diseases associated with connective tissue destruction.
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PMID:Interactions among rheumatoid synovial cells and monocyte-macrophages: production of collagenase-stimulating factor by human monocytes exposed to concanavalin A or immunoglobulin Fc fragments. 624 27

Fc fragments of human IgG can stimulate resident mouse macrophages in culture to secret collagenase, to increase PGE2 secretion, and to decrease the secretion of lysozyme. Active synthesis and secretion were shown by the progressive accumulation of these products in the extracellular medium and inhibition of secretion by cycloheximide. A dose-dependent effect of Fc fragments was demonstrable. Brief exposure of cells to Fc fragments was sufficient to cause the macrophages to secrete collagenase and large amounts of PGE2 for prolonged periods of time, suggesting that a sustained activation rather than temporary modulation of the cells had occurred. Con A had similar effects on macrophage secretory activity. These findings indicate that proteins that bind to specific macrophage plasma membrane receptors may stimulate the secretion of products that promote the inflammatory response.
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PMID:Regulation by Fc fragments of the secretion of collagenase, PGE2, and lysozyme by mouse peritoneal macrophages. 624 97

Ionic iron, as the chelate FeNTA, was taken up by rabbit synovial fibroblasts in monolayer culture. Uptake was accompanied by increased production of latent collagenase and PGE2. Concomitant addition of desferrioxamine, a specific chelator of Fe+++, prevented iron uptake and induction of collagenase and PGE2. Collagenase induced by iron may have a role in the pathogenesis of certain disease states associated with abnormal iron deposition.
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PMID:Iron increases collagenase production by rabbit synovial fibroblasts. 625 9

On the basis of recent in vitro studies, the authors hypothetize on the mechanism of joint destruction in rheumatoid arthritis. They suggest that the leading part is played by the cells of the synovial membrane, which have been found in cultures to secrete biochemical substances, such as collagenase or PGE2, involved in the destruction of articular surfaces. The secretion of these substances is considerably increased by soluble factors produced by monocytes under the influence of lymphocytes, and lymphocytes are known to participate in the chronic inflammatory reaction characteristic of the disease. Such a pathogenic sequence might lead to new therapeutic approaches.
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PMID:[Destruction and inflammation of the joints in rheumatoid arthritis: a pathogenic hypothesis (author's transl)]. 626 Dec 19

The gross morphologic features, histologic features, and synthesis of collagenase and prostaglandin E2 by rheumatoid synovial cells injected into athymic nude mice were studied. A single cell suspension of 2 X 10(7) cells was inoculated subcutaneously into the dorsum of each mouse. In 8 out of 9 mice injected with cells from 6 different patients, rheumatoid synovial cells remained at the injection site for 20-30 days. During this time they became organized into a pannuslike structure with fibroblasts, occasional multinucleated cells, numerous blood vessels, and diffuse collagen fibers. No lymphocytes were seen. Compared with cells cultured in vitro at Day 0, removal, dissociation, and culture of the implanted material at Day 21 revealed a decrease in the percentage of dendritic (stellate) cells known to be associated with collagenase and PGE2 production. However, cells passed through nude mice retained the ability to synthesize both of these compounds. Implantation of rheumatoid synovium into nude mice may provide a way of studying factors influencing the proliferative and destructive lesion of rheumatoid arthritis.
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PMID:Survival of rheumatoid synovium implanted into nude mice. 626 97


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