Cross-Talk of Liver Cells in Response to Endotoxin

Abstract

The gastrointestinal tract is a reservoir of viable bacterial organisms and biologically active microbiological products, such as endotoxin. Endotoxin is the general term for a class of lipopolysaccharide (LPS) molecules located in the outer cell membrane of gram-negative bacteria. Endotoxin constitutes physiological constituent of portal-venous blood (Jacob et al. 1977), and under normal conditions, in contrast to extrahepatic tissues, it does not cause hepatic inflammation. However, an abnormally high release of endotoxin from gram-negative bacteria results in sepsis (defined as the systemic response to bacteremia) and its complications: systematic inflammatory response syndrome (SIRS) and septic shock characterized by hypotension, vascular injury, disseminated intravascular coagulopathy, multiple organ failure, and ultimately death (Parillo 1993). Many mediators, such as cytokines, eicosanoids, PAF, activators of complement cascade, reactive oxygen species, nitric oxide, kinins, thrombin, procalcitonin, and endothelin-1, participate in the pathogenesis of sepsis (Parillo 1993). Due to its integral role in metabolism and host defense mechanisms, the liver is a major organ responsible for initiation of multiple organ failure during sepsis. It is also one of the major organs damaged during endotoxic shock. Endotoxin-triggered inflammatory response in the liver is associated with many structural and functional changes such as early depression of hepatocellular function, activation of parenchymal and nonparenchymal cells, platelet aggregation, intravenous thrombosis, and infiltration of polymorphonuclear leukocytes, mainly neutrophils (Hewett and Roth 1993).