Gram‐negative bacterial lipopolysaccharide impairs hyaluronan clearance in vivo and its uptake by the isolated, perfused rat liver

Ion V. Deaciuc, Gregory J. Bagby, Charles H. Lang, Nebojsa Skrepnik, John J. Spitzer

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Abstract

The purpose of this investigation was to examine the effect of gram‐negative bacterial lipopolysaccharide on hyaluronan concentration in blood plasma, hyaluronan removal from the blood and hyaluronan uptake by isolated, perfused rat liver. Intravenous administration of Escherichia coli lipopolysaccharide to rats markedly increased plasma hyaluronan concentration in a dose‐dependent manner. One day after lipopolysaccharide challenge (0.1 or 1.0 mg per 100 gm body wt), plasma hyaluronan levels were 570.7 ± 66.8 ng. ml−1 and 1,951.0 ± 120.3 ng ml−1, respectively, as compared with 94.2 ± 12.2 ng. ml−1 in time‐matched control animals. Removal of intravenously injected hyaluronan (30 μg per 100 gm body wt) was suppressed 32% by lipopolysaccharide administration (100 μg per 100 gm body wt). At the same dose, lipopolysaccharide induced a severe inhibition (60% to 80%) of hyaluronan uptake by perfused livers isolated 3 or 24 hr after lipopolysaccharide administration. The inhibitory effect of lipopolysaccharide on hyaluronan uptake by the isolated, perfused liver was not abolished by pretreatment with either antibodies to tumor necrosis factor–α IgG or indomethacin, an inhibitor of the cyclooxygenase pathway. Continuous intravenous infusion of recombinant murine tumor necrosis factor–α for 18 to 20 hr did not affect plasma hyaluronan concentration. These data suggest that neither tumor necrosis factor–α, an early cytokine induced by lipopolysaccharide, nor prostaglandins are involved in the mechanism of lipopolysaccharide‐induced inhibition of hyaluronan uptake by the perfused rat liver. Although the mechanism of such inhibition remains to be elucidated, we conclude that gram‐negative bacterial lipopolysaccharide produces lesions at the level of hepatic sinusoidal endothelial cells, impairing their capacity to remove circulating hyaluronan. (HEPATOLOGY 1993;18:173–178).

Original languageEnglish (US)
Pages (from-to)173-178
Number of pages6
JournalHepatology
Volume18
Issue number1
DOIs
StatePublished - Jul 1993

All Science Journal Classification (ASJC) codes

  • Hepatology

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