Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Effects of neutrophil elastase and other proteases on porcine aortic endothelial prostaglandin I2 production, adenine nucleotide release, and responses to vasoactive agents

LeRoy, E. C., Ager, Ann and Gordon, J. L. 1984. Effects of neutrophil elastase and other proteases on porcine aortic endothelial prostaglandin I2 production, adenine nucleotide release, and responses to vasoactive agents. The Journal of Clinical Investigation 74 (3) , pp. 1003-1010. 10.1172/JCI111467

[img]
Preview
PDF - Published Version
Download (1MB) | Preview

Abstract

The effects of neutrophil elastase on endothelial prostacyclin (PGI2) production, nucleotide release, and responsiveness to vasoactive agents were compared with the effects of cathepsin G (the other major neutral protease of neutrophils), pancreatic elastase, trypsin, chymotrypsin, and thrombin. PGI2 production by pig aortic endothelial cells cultured on microcarrier beads and perfused in columns was stimulated in a dose-dependent manner by trypsin, chymotrypsin, and cathepsin G (1-100 micrograms/ml for 3 min). Thrombin, while active at low concentrations (0.1-10 National Institutes of Health U/ml), induced smaller responses. Neutrophil and pancreatic elastase had little or no effect on PGI2 production. Dose-dependent, selective release of adenine nucleotides was induced by neutrophil elastase (3-30 micrograms/ml). The other proteases were much less active; for example, trypsin (100 micrograms/ml) induced a response only approximately 5% as great as did 30 micrograms/ml neutrophil elastase. After exposure to 30 micrograms/ml neutrophil elastase, cells did not exhibit the characteristic burst of PGI2 production in response to extracellular ATP; responsiveness gradually returned after 40-120 min. This effect was not seen with the other proteases. Elastase partly inhibited responses to bradykinin and had no effect on PGI2 production that was stimulated by ionophore A23187. There was no evidence of cytotoxicity, as measured by release of lactate dehydrogenase. Neutrophil degranulation can generate concentrations of elastase and cathepsin G comparable with those tested in the present study, and the effects of these enzymes on endothelial function lead us to suggest that they may play a role in vasoregulation and vascular pathology.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0021-9738/ (accessed 24/02/2014)
Publisher: American Society for Clinical Investigation
ISSN: 0021-9738
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 04:15
URI: http://orca.cf.ac.uk/id/eprint/35574

Citation Data

Cited 59 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics