Effect of plant Kunitz inhibitors from Bauhinia bauhinioides and Bauhinia rufa on pulmonary edema caused by activated neutrophils.
Mediators released from polymorphonuclear neutrophils, in particular elastase, are known to induce acute edematous lung injury. In this study we show that the pulmonary edema in isolated perfused rabbit lungs caused by activated neutrophils via release of elastase is significantly decreased by the Kunitz-type Inhibitor BbCI (10(-5) M) from Bauhinia bauhinoides to the same degree as by eglin C (10(-5) M) from Hirudo medicinalis, which was used as a reference. The highly homologous proteinase inhibitor BrPI (10(-5) M) from Bauhinia rufa, however, did not reduce edema formation. The major difference between these inhibitors is the much higher Ki value of BrPI (Ki = 38 nM) for elastase compared to BbCI (Ki = 5.3 nM) and eglin C (Ki = 0.2 nM), respectively. Elastase liberation from activated PMNs was not influenced by the inhibitors. Our results indicate that BbCI can be a useful tool to study the role of neutrophil elastase in pathophysiological processes.
Neuhof
Christiane
C
Department of Internal Medicine, Justus-Liebig-University of Giessen, Klinikstrasse 36, D-35392 Giessen, Germany.
Oliva
Maria Luiza V
ML
Maybauer
Dirk
D
Maybauer
Mark
M
de Oliveira
Cleide
C
Sampaio
Misako U
MU
Sampaio
Claudio A M
CA
Neuhof
Heinz
H
D000818:Animals; D036481:Bauhinia; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D010940:Plant Proteins / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D011817:Rabbits
C434623:BbKI protein, Bauhinia bauhinioides; C053865:Kunitz-type protease inhibitor, plant; D010455:Peptides; D010940:Plant Proteins; D019272:Leukocyte Elastase