Hepatocytes modulate the hepatic microvascular phenotype.

The liver microvasculature is unique among epithelial organs because it is composed of sinusoids rather than capillaries. Since hepatocytes lack a basement membrane, they are not separated from plasma by any continuous filtration barrier. During the cirrhotic process, the sinusoids become transformed into typical continuous capillaries with specialized endothelial junctions, continuous basement membrane, and pericytes. To explore the factors that determine the phenotype of the hepatic microvasculature, we implanted fetal rat liver fragments onto the chorioallantoid membrane of 6-day-old, shell-less, quail embryos. After 5 days in culture they were studied by light and electron microscopy immunohistochemistry using markers specific for: quail cells, hepatocytes, and basement membrane components of murine or avian origin. The normal quail chorioallantoid membrane is vascularized by continuous capillaries. The periphery of the transplanted fetal rat liver fragments becomes vascularized by microvessels of quail origin. However, the quail microvessels in the proximity of rat hepatocytes assume a sinusoidal phenotype with fenestrations lacking diaphragms, endothelial cell gaps, and devoid of basement membrane. These results demonstrate that liver cells modulate the phenotype of the hepatic microvascular. Since hepatocytes and endothelium do not establish direct cell contacts, we postulate that this modulation is exerted either by secreted soluble cytokines or by the extracellular matrix.