Abstract:
:Proteolysis of connective tissue by enzymes such as PMN-elastase (PMNE) is a crucial step during inflammation and metastasis. Semisynthetic sulfated carbohydrates (SC) were shown to exhibit potent antiinflammatory and antimetastatic activity in vivo. The aim of the present study was to examine whether interferences with PMN-elastase may contribute to these effects. Therefore, the interactions of these compounds with PMNE were evaluated in various test systems. Besides semisynthetic alpha-1,4/1,6- and beta-1,3-glucan sulfates, UFH, a LMWH and pentosan polysulfate (PPS) were included in the study. The inhibitory activity of SC improves not only with increasing molecular weight (MW 10 - 250 kDa: 37 - 54% inhibition at 0.25 micro g/ml) and degree of sulfation (DS 0.25 - 2.0: 16 - 50% inhibition at 0.25 micro g/ml), but depends also on their genuine polysaccharide structure (IC50 beta-1,3-glucan sulfate 0.18 / alpha-1,4/1,6-glucan sulfate 0.25 / UFH 0.5 micro g/ml). Using physiological substrate assays (collagen, elastin), beta-1,3- and alpha-1,4/1,6-glucan sulfates are more active than UFH (inhibition at 1.5 micro g/ml: 41 / 32 / 12%). According to enzyme-inhibitor binding studies, SC exhibit structure dependent affinity to the enzyme (K(d) for PMNE: beta-1,3 < alpha-1,4/1,6 < UFH). Finally, SC were shown to inhibit cancer cell-mediated elastinolysis.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Becker M,Franz G,Alban Skeywords:
subject
Has Abstractpub_date
2003-05-01 00:00:00pages
915-25issue
5eissn
0340-6245issn
2567-689Xpii
03050915journal_volume
89pub_type
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
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更新日期:2002-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:2001-11-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:1994-10-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-02-01 00:00:00
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journal_title:Thrombosis and haemostasis
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更新日期:1999-01-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:1993-11-15 00:00:00
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journal_title:Thrombosis and haemostasis
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更新日期:2000-06-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
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journal_title:Thrombosis and haemostasis
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