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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1993-5-26
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pubmed:abstractText |
Secretory leukocyte inhibitor (SLPI) is a potent inhibitor of serine proteinases, but sensitive to oxidative inactivation due to a methionine residue in the active centre of the inhibitor. We compared the potency of an oxidation-resistant mutant of recombinant SLPI with native recombinant SLPI in lipopolysaccharide (LPS)-induced emphysema in the hamster. Application of this oxidation-resistant mutant reduced the induced emphysema by 70 and 85% in two separate series of experiments. In contrast, an equal amount of native rSLPI resulted in significantly lower inhibition, 30 and 23%, respectively (P = 0.002). To demonstrate the effect of oxygen radicals upon a single LPS instillation in the lungs, we measured anti-neutrophil elastase activity in lung lavage fluid at 10 and 24 h after the instillation of a mixture of LPS and native rSLPI. We found that residual native rSLPI was only 70 and 55% active, respectively. The rSLPI-mutant remained 93% active in a similar experiment. The native and mutant inhibitor showed equal potency against proteinases in a granule extract of hamster neutrophils. We conclude that the replacement of methionine by leucine in the inhibitory centre of rSLPI results in a decreased sensitivity to oxidative inactivation and that this alone is sufficient to explain the greater efficiency of the rSLPI-mutant in reducing the extent of LPS-induced emphysema.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Proteinase Inhibitory Proteins...,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Proteinase Inhibitors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0952-0600
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
33-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8097418-Animals,
pubmed-meshheading:8097418-Chemotaxis, Leukocyte,
pubmed-meshheading:8097418-Cricetinae,
pubmed-meshheading:8097418-Emphysema,
pubmed-meshheading:8097418-Lipopolysaccharides,
pubmed-meshheading:8097418-Mesocricetus,
pubmed-meshheading:8097418-Mutation,
pubmed-meshheading:8097418-Neutrophils,
pubmed-meshheading:8097418-Oxidation-Reduction,
pubmed-meshheading:8097418-Proteinase Inhibitory Proteins, Secretory,
pubmed-meshheading:8097418-Proteins,
pubmed-meshheading:8097418-Reactive Oxygen Species,
pubmed-meshheading:8097418-Recombinant Proteins,
pubmed-meshheading:8097418-Serine Proteinase Inhibitors
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pubmed:year |
1993
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pubmed:articleTitle |
Potency of an oxidation-resistant mutant of secretory leukocyte proteinase inhibitor in lipopolysaccharide-induced emphysema in hamsters.
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pubmed:affiliation |
Department of Pulmonology, University Hospital Leiden, The Netherlands.
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pubmed:publicationType |
Journal Article,
In Vitro
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