Escherichia coli lipopolysaccharide effects on proliferating rat liver cells in culture: a morphological and functional study

Liver cells have been implicated in playing an important role in the pathog enesis of endotoxic shock-associated liver injury. The present study was de signed to investigate Escherichia coli 0111:B4 lipopolysaccharide (LPS) eff ects on proliferating rat liver cells in culture. Isolated cell system can rarely serve as models of complete organisms, but with using an in vitro te st-model, endogenic factors (e,g, hormonal effects, nervous influences, blo od activation, etc.) or experimental stress in laboratory animals can be el iminated as variables affecting hepatocellular responses. In the proposed i n vitro model, using specially proliferating liver cells, morphological cel l alterations were observed after 30 min and low doses endotoxin administra tion (10 mu g/ml). LPS induced an extreme fragility and a diminished adhesi on capacity on cells, Cell-to-cell contacts were also disturbed. The LPS tr eatment produced extreme heterogeneity in liver cell size, enlargement of n uclei, nuclear and cytoplasmic protrusions, and increased the number of lar ge nucleoli and lipid droplets, also decreasing the angiotensin action on i ntracellular calcium levels. The effects observed after the LPS exposition can be related with an altered metabolism of the liver cells in culture due to a destabilization of plasma membrane, a transmembrane signalling altera tion, and a mitochondrial damage. The specificity of cell response to endot oxic lipopolysaccharide suggests a multiple membrane damage inducing import ant metabolic disturbances.