Selective inactivation of human neutrophil elastase by synthetic tannin.
Tannins of natural or synthetic origin are well-known adjuvants in topical anti-inflammatory therapy of skin diseases. In this study, the influence of synthetic tannin on neutrophil accumulation, enzyme release, and on the proinflammatory activity of neutrophil-derived enzymes was investigated. The results show that synthetic tannin (Tamol) specifically inhibits the neutrophil serine protease human leukocyte elastase (HLE) in an irreversible manner with a half-maximal inhibitory concentration (IC50) of 0.3 microgram/ml. Exogenous protein partially abolished the tannin-dependent HLE inhibition (IC50 of Tamol at 1% protein-concentration:1.0 microgram/ml). Synthetic tannin did not influence the activities of other neutrophil enzymes like Cathepsin G, beta-glucuronidase, and myeloperoxidase. The specificity of Tamol for HLE was further substantiated by the lack of inhibition of other serine proteases. Additionally, Tamol had no effect on f-met-leu-phe-induced neutrophil chemotaxis and did not alter enzyme degranulation of neutrophils in response to f-met-leu-phe and opsonized zymosan. We conclude from our results that the anti-inflammatory properties of synthetic tannin may at least in part be due to inactivation of the proinflammatory protease HLE.
Mrowietz
U
U
Department of Dermatology, University of Kiel, Germany.
Ternowitz
T
T
Wiedow
O
O
D015550:Cell Degranulation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002918:Chymotrypsin / Q000378:metabolism; D003179:Complement C3b / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000097:blood*; D013634:Tannins / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
D013634:Tannins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003179:Complement C3b; D015054:Zymosan; D005966:Glucuronidase; D002918:Chymotrypsin; D010196:Pancreatic Elastase