title: Liver sinusoidal endothelial cells and acute non-oxidative hepatic injury induced by Pseudomonas aeruginosa pyocyanin.
abstract: The liver sinusoidal endothelial cell (LSEC) is damaged by many toxins, including oxidants and bacterial toxins. Any effect on LSECs of the Pseudomonas aeruginosa virulence factor, pyocyanin, may be relevant for systemic pseudomonal infections and liver transplantation. In this study, the effects of pyocyanin on in vivo rat livers and isolated LSECs were assessed using electron microscopy, immunohistochemistry and biochemistry. In particular, the effect on fenestrations, a crucial morphological aspect of LSECs was assessed. Pyocyanin treatment induced a dose-dependent reduction in fenestrations in isolated LSECs. In the intact liver, intraportal injection of pyocyanin (11.9 microM in blood) was associated with a reduction in endothelial porosity from 3.4 +/- 0.2% (n = 5) to 1.3 +/- 0.1% (n = 7) within 30 min. There were decreases in both diameter and frequency of fenestrations in the intact endothelium. There was also a decrease in endothelial thickness from 175.8 +/- 5.8 to 156.5 +/- 4.0 nm, an endothelial pathology finding previously unreported. Hepatocyte ultrastructure, liver function tests and immunohistochemical markers of oxidative stress (3-nitrotyrosine and malondialdehyde) were not affected. Pyocyanin induces significant ultrastructural changes in the LSEC in the absence of immunohistochemical evidence of oxidative stress or hepatocyte injury pointing to a novel mechanism for pyocyanin pathogenesis.
authors.affiliation: Centre for Education and Research on Ageing and ANZAC Research Institute, University of Sydney and Concord RG Hospital, Concord, NSW, Australia. rcheluvappa@med.usyd.edu.au
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Cheluvappa
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Cogger
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kwun
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: O'Reilly
authors.forename: David G
authors.initials: DG
authors.lastname: Le Couteur
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Hilmer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D042783:Endothelial Cells / Q000187:drug effects* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008099:Liver / Q000382:microbiology / Q000648:ultrastructure*; D008107:Liver Diseases / Q000382:microbiology / Q000473:pathology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress; D011552:Pseudomonas Infections / Q000473:pathology*; D011550:Pseudomonas aeruginosa; D011710:Pyocyanine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
chemical_list: D011710:Pyocyanine