[Inhibition of eosinophil peroxidase release by chymotrypsin type protease inhibitors from activated human eosinophils].
Eosinophils contain many cytotoxic mediators including eosinophil peroxidase (EPO) in their granules and these mediators are released by various pathophysiological stimuli, resulting in severe damage to various epithelia. However, little is known about the intracellular mechanism of the degranulation. Here we report that eosinophils isolated from patients with bronchial asthma who were not taking corticosteroid hormone had significant amidolytic activities on Suc-Ala-Ala-Pro-Phe-MCA, and also that the activity was completely inhibited by chymostatin (1 x 10(-4) M), eglin C (1 x 10(-4) M), and peptide boronic acid (1 x 10(-4) M), indicating that eosinophils contain a chymotrypsin-like serine protease in the fraction eluted in 50 mM potassium phosphate buffer, pH 8.0 containing 2 M NaCl. Among the various types of protease inhibitors examined, one of the chymotrypsin-type proteases chymostatin (1 x 10(-4) M), but none of the other types of proteases such as leupeptin and E-64, markedly inhibited the EPO release (c.a. 60%) from eosinophils stimulated by immunoglobulin-G (2.5 mg protein/ml beads) in the presence of rhIL-5 (10 ng/ml) or platelet-activating factor (1 x 10(-7) M), although it had no effect on the release by calcium ionophore A23187 (1 x 10(-7) M).
Kawaji
K
K
Third Department of Internal Medicine, University of Tokushima, School of Medicine.
Matsunaga
Y
Y
Kido
H
H
Ogura
T
T
D000328:Adult; D001249:Asthma / Q000097:blood; D002478:Cells, Cultured; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000201:enzymology*; D006801:Humans; D008875:Middle Aged; D010544:Peroxidases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*
D011480:Protease Inhibitors; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D002918:Chymotrypsin