Development of intrahepatic bile ducts in humans. Immunohistochemical study using monoclonal cytokeratin antibodies.

Cytokeratins (CKs) are major structural proteins of intermediate filaments of epithelia. Recent availability of monoclonal antibodies (MoAbs) against various CK polypeptides has made it possible to study their development during cellular differentiation. We analyzed the expression of CKs in the human liver during development. Twenty-four liver specimens were tested by the avidin-biotin complex immunohistochemical method by using three MoAbs against different CK polypeptides (CAM 5.2 against CKs 50, 43, and 39 kd; AE1 against acidic CKs 56.5, 50/50', 48, and 40 kd; and 34 beta E12 against CKs 58, 56.5, and 56 kd). Liver parenchymal cells in fetuses as early as 4 weeks of gestational age reacted with MoAbs CAM 5.2 and AE1, but the expression of AE1-positive CK polypeptides in hepatocytes disappeared by 24 weeks of gestational age. Small cells, presumably ductal plate cells, in direct contact with mesenchyme around the portal vein and along the branches of portal veins, showed strong staining with MoAbs CAM 5.2, AE1, and 34 beta E12, identical to that of bile ducts. In neonates, children, and even in adults, residual MoAbs CAM 5.2-,Ae1, and 34 beta E 12-positive cells were present around the branches of portal veins. These findings suggested that the CK profile of liver parenchymal cells changes during their differentiation into hepatocytes, whereas that of ductal plate cells and bile ducts remains unaltered with respect to the polypeptides tested here. Some ductal plate cells may persist in neonates, children, and even in adults.