Abstract |
Human secretory leukocyte protease inhibitor (SLPI) is a predominant physiologic inhibitor of elastase and cathepsin G, proinflammatory serine proteases released by activated neutrophils. In order to fully evaluate the potential pharmacologic efficacy of human SLPI in animal models of inflammation, it is critical to know the potency of the inhibitor for corresponding proteases from the species of interest. In this report, we compare the inhibitory activity of human and murine SLPI against elastase and cathepsin G from both species. Human and murine neutrophil elastase and cathepsin G display comparable Km values for their specific peptide substrates. Murine SLPI inhibits murine neutrophil elastase and cathepsin G with Ki values of 5 and 0.12 nM, respectively, while human SLPI inhibits the both murine serine proteases with Ki's of 0.02 nM. In contrast, murine SLPI inhibits human neutrophil elastase and cathepsin G with Ki values of 1.4 and 90 nM, respectively, while human SLPI inhibits the proteases with Ki's of 0.3 and 10 nM, respectively. These results demonstrate species-specific variations in the protease inhibitory activities of SLPI. Such variations should be considered in the evaluation of the activity of human SLPI in murine pharmacologic models.
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Authors | C D Wright, J A Kennedy, R J Zitnik, M A Kashem |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 254
Issue 3
Pg. 614-7
(Jan 27 1999)
ISSN: 0006-291X [Print] United States |
PMID | 9920787
(Publication Type: Journal Article)
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Copyright | Copyright 1999 Academic Press. |
Chemical References |
- Proteinase Inhibitory Proteins, Secretory
- Proteins
- SLPI protein, human
- Secretory Leukocyte Peptidase Inhibitor
- Serine Proteinase Inhibitors
- Slpi protein, mouse
- Cathepsins
- Serine Endopeptidases
- CTSG protein, human
- Cathepsin G
- Ctsg protein, mouse
- Leukocyte Elastase
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Topics |
- Animals
- Cathepsin G
- Cathepsins
(metabolism)
- Humans
- Leukocyte Elastase
(metabolism)
- Mice
- Neutrophils
(drug effects, enzymology)
- Proteinase Inhibitory Proteins, Secretory
- Proteins
(pharmacology)
- Secretory Leukocyte Peptidase Inhibitor
- Serine Endopeptidases
- Serine Proteinase Inhibitors
(pharmacology)
- Substrate Specificity
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