The development of the intrahepatic bile ducts in man: A keratin-immunohistochemical study

Abstract

The development of the intrahepatic bile ducts in man was studied using an immunohistochemical technique on 56 liver specimens ranging in age from 6 weeks of gestation to 8 months after birth. On paraffin sections, two monoclonal anticytokeratin antibodies (CAM 5.2 and KL-1) that normally stain both hepatocytes and bile duct cells and two polyclonal anticytokeratin antisera that in normal adult liver stain bile ducts only were applied. For immunohistochemical staining of cryostat sections (only available from 14 weeks of gestation on), four monoclonal antibodies specifically directed against individual cytokeratin polypeptides 7,8, 18 and 19 were used. Adult human hepatocytes contain cytokeratin 8 and 18 whereas bile duct cells also express cytokeratin 7 and 19 in addition to cytokeratin 8 and 18. On paraffin sections, primitive hepatocytes were stained with monoclonal antibodies CAM 5.2 and KL-1 from 6 weeks of gestation on. On cryostat sections, they were positive with monoclonal antibodies anticytokeratin 8 and 18 from the earliest time point examined (14 weeks). From 9 weeks of gestation on, portal vein branches were surrounded by a layer of cells showing a stronger positive reaction with monoclonal antibodies CAM 5.2 and KL-1 on paraffin sections and with monoclonal antibodies anti-cytokeratin 8 and 18 on cryostat sections (only available from 14 weeks on). This layer, referred to as the ductal plate, first appeared around large portal vein branches close to the hilum and subsequently around more peripheral branches. The duct plates became duplicated over variably long segments of their perimeter, lumina appeared and tubular structures were formed. The latter gradually became incorporated in the connective tissue surrounding the portal vein, resulting in the appearance of individualized bile ducts. Ductal plate cells were stained by both polyclonal anticytokeratin antisera on paraffin sections. On cryostat sections (available from 14 weeks of gestation on), they were immunoreactive for cytokeratin 19 but negative with the monoclonal antibody directed against cytokeratin 7 until 20 weeks of gestation. From then on, weakly positive staining for cytokeratin 7 was detected, but staining intensity subsequently increased and reached the level observed in adult liver at 1 month after birth. At birth, the smallest branches of the portal vein were still surrounded by a discontinuous ductal plate. We conclude that intrahepatic bile duct cells develop from hepatocytes around branches of the portal vein.(ABSTRACT TRUNCATED AT 400 WORDS)

Bile Ductule Formation in Fetal, Neonatal, and Infant Livers Compared With Extrahepatic Biliary Atresia

“…We also observed ductular keratins 8 and 18) to express ductular cytokeratins (cytokeratins 8 and 18 / 17 and 19) as they develop to become bile ductular cells. [13][14][15][16][17] To determine if the cells of the limiting ary atresia cases. The control ductules failed to show PCNA plate are capable of actual proliferation during fetal liver staining in their nuclei, but, in biliary atresia, a low level of development, we double-stained our specimens with PCNA PCNA staining was consistently observed.…”

“…[13][14][15][16][17][18][19][20][21][22][23] These studies have further supported the hepadevelopment remains a subject of controversy, although tocytogenic theory. there has been recent evidence that they form from heCytokeratins are the intermediate filaments of the cypatocytes.…”

Human ductal plate and its derivatives express antigens of cholangiocellular, hepatocellular, hepatic stellate/progenitor cell, stem cell, and neuroendocrine lineages, and proliferative antigens

“…They are abortions (spontaneous and artificial), intrauterine fetal death, and autopsies. The gestational ages (weeks) of the 32 fetal livers were as follows: 17,18,19,21,23,24,26,29,30,36,38, and 40. The sex was unclear.…”

The amazing universe of hepatic microstructure†

“…MarieJosé Vanstapel discovered that cholangiocytes are marked by immunostaining for S-100 protein 17 and for keratins using polyclonal antikeratin antiserum. 18 Peter Van Eyken subsequently demonstrated by use of monoclonal antibodies against individual keratins that hepatocytes express keratin 8 (K8) and K18, whereas cholangiocytes express K7 and K19, 19 in addition, thus providing the basis for cell lineage studies in embryonic development of intrahepatic bile ducts 20,21 and in HCCs. 22,23 During embryonic development, K19 is not only a marker of cholangiocytes, but of primitive hepatoblasts as well, 24 and the liver cancer studies revealed that many tumors which were morphologically diagnosed as HCCs express bile duct-type K7 and/or K19, indicating a nonhepatocellular trait in HCCs.…”