Hepatocyte growth factor prevents lipopolysaccharide-induced hepatic sinusoidal endothelial cell injury and intrasinusoidal fibrin deposition in rats

Background. Acute endotoxemia is known to cause activation of Kupffer cells as well as serious injury in parenchymal and nonparenchymal cells in the l iver. We have recently shown that a continuous recombinant hepatocyte growt h factor (rHGF) supply prevents lipopolysaccharide (LPS)-induced liver inju ry in rats. As an attempt to elucidate the mechanism, here we investigate t he cytoprotective effect of rHGF on sinusoidal endothelial cells (SECs) in LPS-induced liver injury in rats. Materials and methods. In order to supply rHGF continuously to the liver, s yngenic rat fibroblasts genetically modified to secret rat rHGF were implan ted in the spleen. Fourteen days after cell implantation, we injected LPS i ntravenously and evaluated SEC damage histologically and blood chemically, Results. Phosphotungstic acid-hematoxylin staining revealed that rHGF treat ment greatly attenuated intrasinusoidal EPS-induced fibrin deposition. The ultrastructural changes in SECs caused by LPS administration in control rat s were barely detectable in rHGF-treated rats. Blood chemical analyses show ed that rHGF potently suppressed the LPS-induced increase in serum hyaluron ic acid and transaminase levels. Conclusions. Our results indicate an important role for HGF in SEC protecti on in vivo and would suggest a novel therapeutic strategy for liver disease s with SEC injury. (C) 1998 Academic Press.