Frequent infiltration of S-100 [protein.sup.+] [CCR5.sup.+] immature dendritic cells in damaged bile ducts of primary biliary cirrhosis compared to cholangiocellular carcinoma

Dendritic cells (DCs) are professional antigen presenting cells that initiate immune responses. We evaluated the relationship between DC infiltration, chemokines/chemokine receptors, and bile duct damage in primary biliary cirrhosis (PBC), compared to cases of cholangiocellular carcinoma arising from the bile duct. Immunohistochemistry revealed significantly more S-100 [protein.sup.+] DCs infiltrating the epithelial layer of bile ducts in PBC than in chronic hepatitis C or control neonatal livers. Furthermore, a higher number of S-100 [protein.sup.+] DCs, but not [fascin.sup.+] or DC lysosomal associated membrane [protein.sup.+] mature DCs, were found in the epithelial layer of the damaged bile ducts of the PBC liver. CC-chemokine receptor (CCR) [5.sup.+] immature DCs frequently accumulated in the portal area in PBC. CCR5 mRNA was also detected in liver tissues from PBC patients by reverse transcription polymerase chain reaction. In situ hybridization revealed the expression of macrophage inflammatory protein (MIP)-1α and MIP-1β mRNA in the epithelial cells of damaged bile ducts. However, no [CD1a.sup.+] immature DCs were found in any of the PBC or chronic hepatitis C specimens or in neonatal liver, whereas they occurred frequently in the cancer nests of cholangiocellular carcinoma, which expressed MIP-3α and were frequently infiltrated by [CCR6.sup.+] DCs. These results indicate that bile ducts damaged by PBC secrete MIP-1α and MIP-1β, while neoplastic ones secrete MIP-3α. They also suggest that [CCR5.sup.+] immature DCs attracted by MIP-1α and MIP-1β may play an important role in the pathogenesis of chronic nonsuppurative destructive cholangitis in PBC. Keywords: chemokines, cholangiocellular carcinoma, chronic nonsuppurative destructive cholangitis, dendritic cell, primary biliary cirrhosis