Mechanism for the Increased Permeability in Endothelial Monolayers Induced by Elastase

[摘要] The aim of this study was to investigate the mechanism for theincrease in endothelial permeability induced by human neutrophilelastase (HNE). Pretreatment of bovine pulmonary artery endothelialcells (BPAEC) with HNE(0-30 μg/ml) for 1 h produced a concentrationdependent increase in125I-albumin clearance. The effect wasreversible and was not due to cytolysis. Pretreatment of BPAEC withsodium tungstate, which depletes xanthine oxidase, or withoxypurinol, did not prevent HNE induced increased permeability.Heparin, which neutralizes the cationic charge of HNE, also had noprotective effect. Pretreatment with heat inactivated HNE, whichstill had positive charge sites, did not result in increasedendothelial permeability. Also, ONO-5046, a novel specific inhibitorof HNE, did prevent increased permeability. These results suggestthat elastase increases endothelial permeability mainly through itsproteolytic effects.

[学科分类] 生理学与病理学