Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1993-5-26
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0952-0600
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Potency of an oxidation-resistant mutant of secretory leukocyte proteinase inhibitor in lipopolysaccharide-induced emphysema in hamsters.
pubmed:affiliation
Department of Pulmonology, University Hospital Leiden, The Netherlands.
pubmed:publicationType
Journal Article, In Vitro