Hyaluronan accumulates around portal vessels in liver after endotoxin treatment of rats

Abstract

Livers of normal rats and rats treated with lipopolysaccharide from Escherichia coli were isolated in situ and tested for capability to extract [³H]-hyaluronan. In control livers, excess unlabeled hyaluronan inhibited extraction of [³H]-hyaluronan both at 4°C and 37°C. Furthermore, part of the [³H]-hyaluronan extracted at 4°C could be released by subsequent perfusion with excess of unlabeled hyaluronan. This behaviour is in accordance with the well-characterized receptor-mediated uptake of hyaluronan in sinusoidal endothelial cells. However, in lipopolysaccharide-treated animals, the uptake of [³H]-hyaluronan was not inhibited by unlabelled polysaccharide, nor could [³H]-hyaluronan bound at 4°C be released from its binding sites. Both types of livers were perfused with 10 μg/ml of hyaluronan and recovered for histology. An accumulation of hyaluronan in areas around portal veins was found in endotoxin treated rats, while only traces of hyaluronan could be visualized in the vessels of normal livers. The location of hyaluronan coincided with cell infiltrates. Thus, there is a different mechanism for liver clearance of hyaluronan in the endotoxic animal.