THE ROLE OF NEUTROPHIL ELASTASE IN HUMAN PULMONARY-ARTERY ENDOTHELIAL-CELL INJURY

Citation
T. Furuno et al., THE ROLE OF NEUTROPHIL ELASTASE IN HUMAN PULMONARY-ARTERY ENDOTHELIAL-CELL INJURY, International archives of allergy and immunology, 112(3), 1997, pp. 262-269
Citations number
17
Categorie Soggetti
Allergy,Immunology
ISSN journal
10182438
Volume
112
Issue
3
Year of publication
1997
Pages
262 - 269
Database
ISI
SICI code
1018-2438(1997)112:3<262:TRONEI>2.0.ZU;2-Y
Abstract
Neutrophils are thought to play a key role in tissue injury. We invest igated the role of human neutrophil-derived elastase in the induction of injury to human pulmonary artery endothelial cells. Incubation of e ndothelial cells with neutrophils increased the release of lactate deh ydrogenase activity, thrombomodulin, and preloaded fura-2 from endothe lial cells, indicating that neutrophils induce endothelial cell injury . Attachment alone of neutrophils to endothelial cells appeared to ind uce activation because elastase release and N-formyl-mentionyl-leucyl- phenylalanine (fMLP)-induced superoxide (O-2(-)) production from neutr ophils incubated with endothelial cells were greater than from neutrop hils only. When endothelial cell were incubated with neutrophils stimu lated by fMLP or phorbol myristate acetate, the amount of elastase in the medium and endothelial cell damage was further enhanced. However w hen neutrophils were blocked from direct attachment to endothelial cel ls using a membrane filter, endothelial cell damage was ameliorated, w hile exogenous neutrophil elastase and medium containing neutrophil-re leased elastase did not induce endothelial cell injury. An inhibitor o f neutrophil elastase, ONO-5046 Na, as well as erythromycin, which red uces neutrophil-derived elastase, dramatically inhibited neutrophil-in duced endothelial cell injury. Superoxide dismutase (SOD) partially in hibited injury. Injury was completely inhibited by treatment with a co mbination of ONO-5046 Na and SOD. These results suggest that attachmen t of neutrophils to endothelial cells is important for endothelial cel l damage and that neutrophil-derived elastase plays an important role in endothelial cell injury in combination with O-2(-). In addition, ON O-5046 Na and erythromycin may be useful in treating diseases worsened by excessive neutrophil activity.