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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rabbit alveolar macrophage secretes at least two collagenolytic metalloproteinases in vitro including an interstitial collagenase and a type V collagenase. Using assays previously shown to discriminate between these two activities, the secretion of these two enzyme activities was investigated. Both enzyme activities accumulated in culture over 11 days and the release of both were similarly inhibited by cycloheximide. Collagenolytic activity was negligible in cell lysates. The interstitial collagenase was found in a latent form but the type V collagenase activity was active in the culture medium. When cultured in the presence of dexamethasone, the secretion of both the enzymes were identically inhibited in a dose-dependent manner. Indomethacin was an effective inhibitor of secretion of both collagenases at a concentration of 10(-5) M but not at lower concentrations. Finally, bacterial lipopolysaccharide stimulated the secretion of both type V and interstitial collagenase by these cells. These studies indicate that, like the interstitial collagenase, the type V collagenase is released from the cell as synthesized and is not stored intracellularly. Protein synthesis is necessary for the release of both these collagenases. Furthermore, the release of type V collagenase responded to dexamethasone, indomethacin, and lipopolysaccharide in a manner identical to the secretion of the interstitial collagenase suggesting that synthesis and secretion of these two enzymes are regulated in a similar manner.
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PMID:Effect of dexamethasone, indomethacin, and lipopolysaccharide on the secretion of interstitial collagenase and type V collagenase by cultured macrophages. 609 75

The lethal action of endotoxin was studied in mice sensitized against the lipopolysaccharide by D-galactosamine. Protection was obtained by FPL 55712, a selective antagonist of sulfidopeptide leukotrienes, by diethylcarbamazine, an inhibitor of leukotriene biosynthesis, by BW 755C, a dual lipoxygenase and cyclooxygenase inhibitor, and by dexamethasone, which inhibits arachidonate release. Indomethacin incompletely antagonized endotoxin lethality; indoprofen did not protect at all. Leukotriene generation induced by endotoxin in vivo could be demonstrated in rats by employing a radioimmunoassay on bile extracts since intravascular sulfidopeptide leukotrienes were rapidly eliminated into bile. Additionally, however, endotoxin affected the hepatobiliary elimination of sulfidopeptide leukotrienes. From intravenously injected tracer [3H]leukotriene D4, 67% appeared only partially metabolized in bile within 30 min in control rats. Endotoxin and lipid A reduced the biliary [3H]leukotriene D4 secretion by up to 80% while enhancing the hepatic [3H]leukotriene D4 content up to twofold. This inhibition of hepatobiliary elimination was stronger than endotoxin-induced reductions of bile flow or of biliary [14C]taurocholate secretion. Endotoxin, as an activator of the arachidonate cascade, thus potentiates its action in vivo by interfering with the rapid hepatobiliary clearance of sulfidopeptide leukotrienes in addition to stimulating leukotriene and prostanoid formation.
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PMID:Role of peptide leukotrienes and their hepatobiliary elimination in endotoxin action. 609 38

The effect of heat-aggregated immunoglobulin G's (HAgg-IgGs) on bacterial lipopolysaccharide- (LPS) induced polyclonal B cell activation (PBA) was studied. HAgg-IgGs (10 micrograms/ml or more) that were added to cultures of spleen cells obtained from BALB/c mice remarkably decreased the numbers of anti-trinitrophenyl (TNP) antibody-producing cells (APC) generated by LPS in cultures. This suppressive effect was seen when HAgg-IgGs were added within 1 hr after the initiation of culture. Later addition of HAgg-IgGs did not cause any effective suppression of the generation of APC. Moreover, the spleen cells, which had been pretreated with HAgg-IgGs, washed for removal of free HAgg-IgGs, and subsequently cultured, responded poorly to LPS. HAgg-IgG2b was more effective than HAgg-IgGs, but HAgg-IgG2a did not have any suppressive effect. A similar suppressive effect was observed when HAgg-IgG2b-Fc was added into culture, whereas none was noted with IgG2b-Fab. Indomethacin (IM), known as cyclooxygenase inhibitor, could completely abrogate the suppressive effects of HAgg-IgGs on LPS-induced PBA responses when it was added to the cell cultures together with HAgg-IgGs or to the cultures of HAgg-IgGs-pretreated cells. Addition of prostaglandin E2 (PGE2) showed strong suppression of the PBA responses of spleen cell cultures that had been pretreated with HAgg-IgGs and IM, but other PG analogues showed no suppression. Thus, it would appear that PGE2 has some role in the suppression of the LPS-induced PBA response.
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PMID:Suppression of lipopolysaccharide-induced polyclonal B cell activation of murine spleen with heat-aggregated murine immunoglobulin G. 622 74

The production of collagenase by lipopolysaccharide-(LPS) activated guinea pig macrophages is mediated by prostaglandins (PG) of the E series. After stimulation of guinea pig macrophages with LPS, extracellular PGE levels and cellular cAMP levels are elevated. Indomethacin inhibits not only PG synthesis, but also cAMP and collagenase production in LPS-stimulated macrophage cultures. In these indomethacin-inhibited cultures containing LPS, dibutyryl (dB) cAMP, or cholera toxin can restore macrophage collagenase production but not PG synthesis. Moreover, dBcAMP and cholera toxin enhance collagenase production in LPS-activated cultures. Initial activation of the macrophages by an agent such as LPS is a prerequisite for synthesis of collagenase, since in the absence of LPS, dBcAMP or cholera toxin alone are ineffective stimuli. These findings clearly demonstrate a role for PG-induced elevations of cAMP in the production of collagenase by LPS-activated macrophages.
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PMID:Mediation of macrophage collagenase production by 3'-5' cyclic adenosine monophosphate. 624 42

Kupffer cells exposed to bacterial lipopolysaccharide in vitro synthesized collagenase and released the major portion of it into the extracellular space while the intracellular level of enzyme was not altered significantly. Cycloheximide prevented the appearance of collagenase in the medium indicating de novo synthesis. Indomethacin, an inhibitor of cyclooxygenase, also blocked collagenase synthesis. In line with this observation. Kupffer cells were found to synthesize substantial amounts of prostaglandin E2 when exposed to lipopolysaccharide; concomitantly, cellular cAMP levels were increased. Indomethacin was shown to abolish the stimulated cAMP formation. Addition to the culture medium of cAMP or dibutyryladenosine 3', 5'-monophosphate as well as of prostaglandin E2 or, to a lesser extent, prostaglandin E1 allowed indomethacin-inhibited cells to resume the production of collagenase. It is proposed that in rat Kupffer cells lipopolysaccharide-elicited collagenase synthesis and excretion is mediated sequentially by stimulated production of prostaglandin E2, enhanced adenylate cyclase activity and increased intracellular cAMP levels.
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PMID:Involvement of prostaglandin E and adenosine 3', 5'-monophosphate in lipopolysaccharide-stimulated collagenase release by rat Kupffer cells. 628 7

The synthesis and secretion of prostaglandins and leukotrienes by mouse peritoneal macrophages is under several regulatory controls. Arachidonic acid must first be released from phospholipid stores by the action of phospholipases. Macrophages have the capacity to deacylate arachidonic acid directly from the SN2 position of phospholipids via the action of a phospholipase A2. In addition, these cells contain a phospholipase C capable of removing inositol-phosphate from phosphatidylinositol generating diacylglycerol. Another enzyme, diacylglycerol lipase is present to then generate arachidonic acid. The free arachidonic acid then enters the cyclooxygenase pathway to generate prostaglandins, the lipoxygenase pathway to generate leukotrienes or both pathways. The nature of the inflammatory stimulus added to these cells determines which of the above pathways become operative. Zymosan and the Ca++ ionophore, A23187 stimulate the synthesis of both prostaglandins and leukotrienes whereas phorbol myristate acetate and lipopolysaccharide induce only the synthesis of prostaglandins. In addition, the synthesis of these two products by macrophages can be regulated by certain antiinflammatory compounds. Indomethacin, aspirin, ibuprofen and benoxaprofen are only inhibitors of the prostaglandin pathway, whereas BW755C, 5,8,11-ETYA, NDGA and sulindac sulfide (high doses) are inhibitors of the synthesis of both prostaglandins and leukotrienes. Dapsone, an effective drug for leprosy, also inhibits the synthesis of both of these products.
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PMID:Physiological and pharmacological regulation of prostaglandin and leukotriene production by macrophages. 632

Leishmania tropica in BALB/c mice causes a fatal infection accompanied by the development of multiple metastatic lesions. Spleen cells from these mice were shown to have depressed proliferative responses to concanavalin A (Con A), phytohemagglutinin (PHA), and lipopolysaccharide (LPS). Coinciding with this immunodepression was the development of a cell population capable of suppressing normal spleen cell responses to Con A. This suppressor cell activity was first observed at 6 wk and was present throughout the remainder of the infection. At 12 wk the suppressor cells could be removed by Sephadex G-10 passage or carbonyl iron treatment; however, Sephadex G-10 passage could not reverse the suppression at 18 wk. Indomethacin, a prostaglandin synthetase inhibitor, was found to abrogate the activity of the adherent suppressor cell, suggesting that prostaglandin production may be involved in the immunosuppression seen in these mice. In addition, Sephadex G-10 passage and indomethacin were found to markedly augment spleen cell responses to leishmanial antigen, indicating that the adherent suppressor cell is capable of regulating specific immunologic responses.
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PMID:Experimental cutaneous leishmaniasis. I. Nonspecific immunodepression in BALB/c mice infected with Leishmania tropica. 645 74

We demonstrated previously that rabbit alveolar macrophages stimulated in vitro by bacterial lipopolysaccharide (LPS) have markedly enhanced procoagulant activity (PCA), caused by increased production of a cell-associated tissue thromboplastin. The present study examined the role of arachidonic acid metabolites in modulating the expression of this PCA. Alveolar macrophages lavaged from normal rabbits were incubated in vitro with LPS, indomethacin, and purified prostaglandins, and the resultant PCA was measured. LPS stimulated a significant increase in macrophage PCA relative to unstimulated controls (p less than 0.01). Indomethacin suppressed the ability of LPS to stimulate PCA in a dose-related fashion. The addition of PGE2 or PGE1 reversed the suppressive action of indomethacin (p less than 0.01), whereas PGF2 alpha, PGD2, TXB2, and 6-keto PGF1 alpha had no such effect. PGE2 did not affect PCA unless the macrophages were also stimulated with LPS. A significant correlation (rs = 0.72, p less than 0.01) existed between the level of LPS-stimulated macrophage PCA and the corresponding amount of immunoreactive PGE2 released into the culture medium. The results of this study demonstrate that PGE is required for the LPS-mediated enhancement of rabbit alveolar macrophage-associated tissue thromboplastin and that PGE can stimulate the expression of PCA by appropriately conditioned cells.
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PMID:Prostaglandin E is required for the augmentation of procoagulant activity of LPS-stimulated rabbit alveolar macrophages. 658 Dec 28

Macrophage-like P388D1 cells, when stimulated with lipopolysaccharide (LPS), produced a factor(s) whose activity was inhibitory to growth of Lewis lung carcinoma cells. Indomethacin, a prostaglandin-synthesis inhibitor, augmented the production of tumoristatic activity by LPS-stimulated P388D1 cells, whereas exogenous prostaglandin E2 (PGE2) suppressed its secretion. These results suggest that P388D1 cells regulate their antitumor abilities by producing PGE2, which inhibits production of soluble factor(s) with tumoristatic activities.
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PMID:Prostaglandin E2 regulation of tumoristatic factor production by macrophage-like P388D1 cells. 659 90

We examined the effect of bovine aortic endothelial cell culture supernatants upon the generation of procoagulant activity by human blood monocytes. Confluent endothelial monolayers were cultured for up to 96 h. At timed intervals, culture supernatants were collected and incubated for 5 h with lipopolysaccharide-stimulated human peripheral blood mononuclear cells. The procoagulant activity of mononuclear cell lysates was determined in a one-stage clotting assay. In five experiments, procoagulant activity with culture supernatant (time 0) was 2,294 +/- 761 U/ml (mean +/- SEM). Culture supernatants from endothelial cells incubated for 24-96 h strongly inhibited mononuclear cell generation of procoagulant activity. Indomethacin (10 microM) added to endothelial cells delayed the appearance of procoagulant inhibitor for 72 h. Bovine aortic smooth muscle cell culture supernatants did not inhibit procoagulant activity. The inhibitor was heat stable, effective at 1:50 dilution, soluble, and acid sensitive, with a molecular weight of less than 1,500. Further studies on subpopulations of mononuclear cells demonstrated that endothelial inhibitor selectively decreased the generation of monocyte procoagulant activity and interfered with T lymphocyte amplification of monocyte production of procoagulant activity. Thus, we have demonstrated that endothelial cells elaborate a potent inhibitor of monocyte procoagulant activity.
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PMID:Bovine aortic endothelial cells elaborate an inhibitor of the generation of lipopolysaccharide-stimulated human blood monocyte procoagulant activity. 673 53


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