FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1569127166> ?p ?o ?g. }

• W1569127166 endingPage "199" @default.
• W1569127166 startingPage "197" @default.
• W1569127166 abstract "Dear Sir, Antithrombin (AT) is an important inhibitor of serine proteases that are part of the coagulation cascade. Recent interest has focused on the anti-inflammatory properties of AT. One mechanism suggested for AT's anti-inflammatory effect is the release of prostacyclin (PGI2). AT has been shown to induce the release of PGI2 in several in vitro and in vivo studies. It stimulated PGI2 production by cultured bovine aortic endothelial cells which was inhibited by anti-AT antiserum and heparin [1Yamauchi T. Umeda F. Inoguchi T. Nawata H. Antithrombin III stimulates prostacyclin production by cultured aortic endothelial cells.Biochem Biophys Res Commun. 1989; 163: 1404-11Crossref PubMed Scopus (132) Google Scholar]. AT increased the release of PGI2 in human umbilical vein endothelial cells. This effect was abolished by addition of heparin and heparinase [2Horie S. Ishii H. Kazama M. Heparin-like glycosaminoglycan is a receptor for antithrombin III-dependent but not for thrombin-dependent prostacyclin production in human endothelial cells.Thromb Res. 1990; 59: 895-904Abstract Full Text PDF PubMed Scopus (121) Google Scholar]. The intravenous administration of AT in rats significantly increased the plasma levels of PGI2. Treatment with heparin and AT had no effect on the release of PGI2[3Uchiba M. Okajima K. Murakami K. Okabe H. Takatsuki K. Effects of antithrombin III (AT III) and Trp49-modified AT III on plasma level of 6-keto-PGF1 alpha in rats.Thromb Res. 1995; 80: 201-8Abstract Full Text PDF PubMed Scopus (56) Google Scholar]. These observations suggested that AT promotes the release of PGI2 by interacting with endothelial heparin-like glycosaminoglycans. However, recent results from Uchiba and Okajima [4Uchiba M. Okajima K. Antithrombin does not directly promote the endothelial production of prostacyclin in cultured endothelial cells.Thromb Haemost. 2001; 86: 722-3Crossref PubMed Scopus (12) Google Scholar] did not support these previous findings; incubation of cultured human umbilical vein endothelial cells (HUVECs) and cultured bovine aortic endothelial cells (BAECs) did not induce PGI2 release. Thus it seems likely that the release of PGI2 by AT is not common to all endothelial cells and the exact mechanism, therefore, is still unclear. At present, AT-induced PGI2 formation and release has not been studied in endothelial microvascular cells. Thus, we incubated primary cultures of human dermal microvascular cells (HDMEC), which are derived from human foreskins (for details see [5Hoffmann G. Schobersberger W. Rieder J. et al.Human dermal microvascular endothelial cells express inducible nitric oxide synthase in vitro.J Invest Dermatol. 1999; 112: 387-90Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar]) with AT (1, 5, 10 and 25 U mL−1 Kybernin P®) for 60, 120, 180, 240 and 480 min, both without as well as with indomethacin (10 µmol L−1). PGI2 release was estimated by measuring its stable analog 6-keto-prostaglandin-F1α (6-keto-PGF1α) with an enzyme-immunoassay (EIA) system (Biotrack, Amersham, Bucks, UK) Incubations of HDMEC with AT at 1, 5 and 10 U mL−1 had no effect on the release of 6-keto-PGF1α in the culture supernatant. Compared with untreated controls, incubation of HDMEC with 25 U mL−1 AT resulted in an increase of 6-keto PGF1α after 180 min (25.5 ± 8.3 pg mL−1 vs. 17.1 ± 6.0 pg mL−1; P= 0.006; n= 6), after 240 min (35.6 ± 12.6 pg mL−1 vs. 23.5 ± 10.1 pg mL−1; P= 0.003; n= 6) and after 480 min (104.8 ± 68.7 pg mL−1 vs. 37.7 ± 11.4 pg mL−1; P= 0.008; n= 6) (Fig. 1). Coincubation of 25 U mL−1 AT with indomethacin completely abolished the release of 6-keto-PGF1α. AT has been suggested to act as an anti-inflammatory agent. In several studies, administration of high concentration of AT improved organ failure and mortality in animals exposed to lipopolysaccharides [6Emerson Jr, T.e. Fournel M.A. Redens T.B. Taylor Jr, F.b. Efficacy of antithrombin III supplementation in animal models of fulminant Escherichia coli endotoxemia or bacteremia.Am J Med. 1989; 87: 27S-33SAbstract Full Text PDF PubMed Scopus (91) Google Scholar, 7Taylor Jr, F.b. Emerson Jr, T.e. Jordan R. Chang A.K. Blick K.E. Antithrombin-III prevents the lethal effects of Escherichia coli infusion in baboons.Circ Shock. 1988; 26: 227-35PubMed Google Scholar]. Clinical studies showed a beneficial effect of high concentrations of AT on the incidence of multiple organ failure in patients with severe sepsis [8Eisele B. Lamy M. Thijs L.G. et al.Antithrombin III in patients with severe sepsis. A randomized, placebo- controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis [see comments].Intensive Care Med. 1998; 24: 663-72Crossref PubMed Scopus (288) Google Scholar, 9Inthorn D. Hoffmann J.N. Hartl W.H. Muhlbayer D. Jochum M. Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction.Shock. 1997; 8: 328-34Crossref PubMed Scopus (119) Google Scholar]. However, a recent study with septic patients maintaining high plasma concentration of AT (150%) by substitution of AT did not result in a reduction of 28-day mortality [10Warren B.L. Eid A. Singer P. et al.Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial.JAMA. 2001; 286: 1869-78Crossref PubMed Scopus (1134) Google Scholar]. One mechanism suggested for the anti-inflammatory effect of AT is the release of prostacyclin (PGI2). AT (250 U kg−1) reduced coagulation abnormalities and pulmonary vascular injury in endotoxin-exposed rats, and this was accompanied by elevated plasma levels of PGI2. These effects were completely inhibited by indomethacin [11Uchiba M. Okajima K. Murakami K. Okabe H. Takatsuki K. Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III.Am J Physiol. 1996; 270: L921-30PubMed Google Scholar]. In a recent study, AT had beneficial effects on ischemia/reperfusion injury of the liver by releasing PGI2[12Harada N. Okajima K. Kushimoto S. Isobe H. Tanaka K. Antithrombin reduces ischemia/reperfusion injury of rat liver by increasing the hepatic level of prostacyclin.Blood. 1999; 93: 157-64Crossref PubMed Google Scholar]. In contrast with others [1Yamauchi T. Umeda F. Inoguchi T. Nawata H. Antithrombin III stimulates prostacyclin production by cultured aortic endothelial cells.Biochem Biophys Res Commun. 1989; 163: 1404-11Crossref PubMed Scopus (132) Google Scholar, 2Horie S. Ishii H. Kazama M. Heparin-like glycosaminoglycan is a receptor for antithrombin III-dependent but not for thrombin-dependent prostacyclin production in human endothelial cells.Thromb Res. 1990; 59: 895-904Abstract Full Text PDF PubMed Scopus (121) Google Scholar], we cannot demonstrate an increase in PGI2 by AT treatment of cultured cells in concentrations which are of clinical relevance. Only by applying excessive doses of AT (25 U mL−1) could a significant increase of PGI2 in the culture supernatant be measured. The reasons for these differences are not clear at present. It seems that there are cell-type specific mechanisms involved in AT-induced PGI2 formation. HDMEC are microvascular endothelial cells derived from human foreskins and are different with regard to cell morphology, proliferation and stimulation by proinflammatory agents as compared with other endothelial cells, e.g. HUVEC, BAEC [13Sepp N. Li L.J. Lee K.H. et al.Basic fibroblast growth factor increases expression of alpha V and beta 3 integrin complex on human microvascular endothelial cells.J Invest Dermatol. 1994; 103: 295-9Crossref PubMed Scopus (118) Google Scholar]. We used early passages (3–6) in order to avoid later dedifferentiation. Whether the release of PGI2 is in fact the crucial mechanism for some of the anti-inflammatory properties of AT seems to be questionable. Dschietzig et al. [14Dschietzig T. Alexiou K. Laule M. et al.Stimulation of pulmonary big endothelin-1 and endothelin-1 by antithrombin III. a rationale for combined application of antithrombin III and endothelin antagonists in sepsis-related acute respiratory distress syndrome?.Crit Care Med. 2000; 28: 2445-9Crossref PubMed Scopus (15) Google Scholar] demonstrated that AT treatment failed to increase PGI2 levels in isolated endotoxin-exposed rat lungs, but augmented release of endothelin 1. Thus, it is possible that mechanisms other than the release of PGI2 are responsible for the anti-inflammatory effects of AT. In conclusion, this study demonstrates that only excessive concentrations of AT release PGI2 in human dermal microvascular cells. Clinically relevant concentrations had no impact. In synopsis with recent data [4Uchiba M. Okajima K. Antithrombin does not directly promote the endothelial production of prostacyclin in cultured endothelial cells.Thromb Haemost. 2001; 86: 722-3Crossref PubMed Scopus (12) Google Scholar], it seems questionable whether the release of PGI2 by AT is a uniform mechanism in the vascular system." @default.
• W1569127166 created "2016-06-24" @default.
• W1569127166 creator A5014318089 @default.
• W1569127166 creator A5023491380 @default.
• W1569127166 creator A5033982043 @default.
• W1569127166 creator A5039724225 @default.
• W1569127166 creator A5057729416 @default.
• W1569127166 date "2003-01-01" @default.
• W1569127166 modified "2023-09-30" @default.
• W1569127166 title "Only excessive III concentrations release prostacyclin in human dermal microvascular cells" @default.
• W1569127166 cites W1576352249 @default.
• W1569127166 cites W1978037685 @default.
• W1569127166 cites W1989077130 @default.
• W1569127166 cites W1999644118 @default.
• W1569127166 cites W2005736107 @default.
• W1569127166 cites W2014755540 @default.
• W1569127166 cites W2051814521 @default.
• W1569127166 cites W2086413498 @default.
• W1569127166 cites W2113481864 @default.
• W1569127166 cites W2115301416 @default.
• W1569127166 cites W2397743218 @default.
• W1569127166 cites W72549793 @default.
• W1569127166 doi "https://doi.org/10.1046/j.1538-7836.2003.00015.x" @default.
• W1569127166 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12871564" @default.
• W1569127166 hasPublicationYear "2003" @default.
• W1569127166 type Work @default.
• W1569127166 sameAs 1569127166 @default.
• W1569127166 citedByCount "0" @default.
• W1569127166 crossrefType "journal-article" @default.
• W1569127166 hasAuthorship W1569127166A5014318089 @default.
• W1569127166 hasAuthorship W1569127166A5023491380 @default.
• W1569127166 hasAuthorship W1569127166A5033982043 @default.
• W1569127166 hasAuthorship W1569127166A5039724225 @default.
• W1569127166 hasAuthorship W1569127166A5057729416 @default.
• W1569127166 hasBestOaLocation W15691271661 @default.
• W1569127166 hasConcept C126322002 @default.
• W1569127166 hasConcept C185592680 @default.
• W1569127166 hasConcept C2781128415 @default.
• W1569127166 hasConcept C71924100 @default.
• W1569127166 hasConcept C98274493 @default.
• W1569127166 hasConceptScore W1569127166C126322002 @default.
• W1569127166 hasConceptScore W1569127166C185592680 @default.
• W1569127166 hasConceptScore W1569127166C2781128415 @default.
• W1569127166 hasConceptScore W1569127166C71924100 @default.
• W1569127166 hasConceptScore W1569127166C98274493 @default.
• W1569127166 hasIssue "1" @default.
• W1569127166 hasLocation W15691271661 @default.
• W1569127166 hasLocation W15691271662 @default.
• W1569127166 hasOpenAccess W1569127166 @default.
• W1569127166 hasPrimaryLocation W15691271661 @default.
• W1569127166 hasRelatedWork W1972407183 @default.
• W1569127166 hasRelatedWork W2103900944 @default.
• W1569127166 hasRelatedWork W2112293469 @default.
• W1569127166 hasRelatedWork W2132328847 @default.
• W1569127166 hasRelatedWork W2345397538 @default.
• W1569127166 hasRelatedWork W2438089724 @default.
• W1569127166 hasRelatedWork W2748952813 @default.
• W1569127166 hasRelatedWork W2754783076 @default.
• W1569127166 hasRelatedWork W2883640684 @default.
• W1569127166 hasRelatedWork W2899084033 @default.
• W1569127166 hasVolume "1" @default.
• W1569127166 isParatext "false" @default.
• W1569127166 isRetracted "false" @default.
• W1569127166 magId "1569127166" @default.
• W1569127166 workType "article" @default.