AJP - Lung Cellular and Molecular Physiology, Vol 257, Issue 4 202-L208, Copyright © 1989 by American Physiological Society
Lung lymph capillary injury-related protease
M. Orlowski and M. Lesser
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, New York 10029.
Capillary damage induced in sheep by intravenous infusion of Escherichia
coli endotoxin, oleic acid, or air emboli causes the appearance in lung
lymph of a serine protease with trypsin-like activity. The time course of
the appearance of the enzyme and the extent of its activity increase
indicate a close association with capillary injury. The enzyme was isolated
from active lymph after a 9,000-fold purification by affinity
chromatography on Reactive Blue-agarose, aprotinin-agarose, and
p-amino-benzamidine-agarose columns. The protein, molecular mass of 70-75
kDa, is composed of two polypeptide chains of 31 and 43 kDa linked by
disulfide bonds. Studies with synthetic peptide and thioester substrates
showed preferential cleavage of substrates having two or more basic amino
acids and the importance for activity of secondary enzyme-substrate
interactions at sites removed from the scissile bond. The specificity of
the enzyme and its pattern of sensitivity to inhibition by a series of
isocoumarin derivatives distinguish it from enzymes of the clotting and
complement systems and also from tissue plasminogen activator and lung and
skin tryptase. The origin of the enzyme, its role in capillary damage, and
its physiological function remain to be established.
