Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-6-5
pubmed:abstractText
The inhibition of human chymase, a chymotrypsin-like proteinase stored in mast cell granules, by secretory leukocyte proteinase inhibitor (SLPI) is investigated in this study. SLPI is a serine proteinase inhibitor present in human mucus secretions and tissues. It binds heparin, a highly sulfated glycosaminoglycan also found in mast cell secretary granules, and the interaction increases its effectiveness as an inhibitor of neutrophil elastase. Analysis of the chymase-SL interaction by equilibrium and kinetic methods indicates that the inhibition of chymase results from the reversible formation of a stable 1:1 enzyme-inhibitor complex. The dissociation equilibrium constant (determined in reactions containing 0.18 M or 1.0M NaCl (pH 8.0, 25 degrees C) was 5 X 10(-8) and 2 x 10(-8) M, respectively. Addition of heparin to the low-salt reaction decreased the Ki approximately 10-fold to a value of 3 x 10(-9) M, making SLPI a more effective inhibitor of human chymase. The decrease was due primarily to an approximately 10-fold increase in the association rate constant (kass) from 2 X 10(4) to 3 X 10(5) M-1 s-1. The magnitudes of the rate and dissociation equilibrium constants indicate that SLPI has the potential to be a good chymase inhibitor in vivo, especially if chymase and heparin are released from mast cell granules simultaneously. The enhanced interaction in the presence of heparin supports the importance of this glycosaminoglycan to the inhibitory function of SLPI.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
327
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
81-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Inhibition of human mast cell chymase by secretory leukocyte proteinase inhibitor: enhancement of the interaction by heparin.
pubmed:affiliation
Department of Dermatology, University of Pennsylvania, Philadelphia 19104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't