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

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... 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 Gramnegative bacterial toxins, with a focus on LSECs. Hyperlipidemia is an important response to Gramnegative 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. ß