Pathogenesis of the hyperlipidemia of Gram-negative bacterial sepsis may involve pathomorphological changes in liver sinusoidal endothelial cells

Rajkumar Cheluvappa, Gerene M. Denning, Gee W. Lau, Michael C. Grimm, Sarah N. Hilmer, David G. Le Couteur

Research output: Contribution to journalReview article

Abstract

The Gram-negative bacterium Pseudomonas aeruginosa is one of the most common opportunistic pathogens, especially after liver transplantation. Pathophysiological alterations of liver sinusoidal endothelial cells (LSECs) have far-reaching repercussions on the liver and on metabolism. LSECs are perforated with fenestrations, pores that facilitate the transfer of lipoproteins and macromolecules between blood and hepatocytes. Gram-negative bacterial endotoxin (lipopolysaccharide, LPS) and the P. aeruginosa toxin, pyocyanin, have marked effects on LSECs. Initial loss of LSEC porosity (defenestration) induced by P. aeruginosa pyocyanin and LPS may confer subsequent immune tolerance to circulating bacterial antigens and toxins. This review collates the known immune responses of the liver to Gram-negative bacterial toxins, with a focus on LSECs. Hyperlipidemia is an important response to Gram-negative bacterial sepsis. The mechanisms proposed for sepsis-associated hyperlipidemia include tissue lipoprotein lipase inhibition and upregulated hepatic triglyceride production. In this review, we propose defenestration of the LSECs by bacterial toxins as an additional mechanism for the hyperlipidemia of sepsis. Given the role of LSECs in hyperlipidemia and liver allograft rejection, LSEC changes induced by P. aeruginosa toxins including LPS and pyocyanin may have significant clinical implications.

Original languageEnglish (US)
Pages (from-to)e857-e867
JournalInternational Journal of Infectious Diseases
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2010

Keywords

  • Electron microscopy
  • Immunohistochemistry
  • Liver sinusoidal endothelial cell fenestrations
  • Oxidative stress
  • Pseudomonas aeruginosa Pyocyanin
  • Transplantation

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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