In vivo experiments involving secretory component in the rat hepatic transfer of polymeric IgA from blood into bile.

Human or rat purified secretory IgA (sIgA) injected intravenously (i.v.) into rats is transferred to bile much less (seven to twenty-four times) than human or rat polymeric IgA (pIgA) devoid of secretory component (SC). A polymeric Fc alpha (pFc alpha) fragment of a human IgAl myeloma protein, obtained by IgA-protease digestion, bound in vitro to rat SC and was actively transferred in vivo into bile, in contrast to the corresponding Fab alpha. The IgA recovered in bile was not degraded, as judged by sedimentation in density gradients. Purified rabbit IgG anti-rat SC antibody was also efficiently transported in vivo into bile, about forty times more than normal rabbit IgG. The biliary transport of anti-Sc antibody could be reduced and retarded by the simultaneous i.v. injection of purified rat SC or human pIgA. The transfer of rat 125I-pIgA into bile was also significantly reduced and retarded by the concomitant i.v. injection of purified rat or human SC. Moreover, i.v. injection of purified rat or human SC induced a marked and prolonged decrease of the sIgA level in the bile. Rat SC was more effective than human SC in this respect. All these in vivo experiments confirm the in vitro findings of Orlans, Peppard, Fry, Hinton : Mullock, (1979) and Socken, Jeejeebhoy, Bazin & Underdown, (1979) showing that Sc is the IgA-receptor on the hepatocyte membrane for the transfer of pIgA from rat plasma into bile

The healthy biliary tree: Cellular and immune biology

The biliary tree is an arborizing system of intra- and extrahepatic conduits connecting the liver to the intestine. The biliary tree has a complex tridimensional structure, encompassing bile ducts of different sizes, morphologies, and functions. The most studied function of biliary epithelial cells (cholangiocytes) is to regulate the hydration and alkalinity of the primary bile secreted by hepatocytes. An increasing number of evidence highlight the ability of cholangiocyte to undergo changes in phenotype, proliferation, and secretory activity in response to liver damage. Cholangiocytes are involved in biliary innate immunity; altered biliary innate immunity plays a role in a number of biliary diseases, including genetic cholangiopathies, such as cystic fibrosis-related liver disease. In addition, cholangiocytes may behave as antigen-presenting cells and secrete immunoglobulins as well as several antimicrobial peptides. Thus, cholangiocytes, by participating actively to the immune and inflammatory responses, represent a first defense line against liver injury from different causes. In fact, cholangiocytes possess a number of sensing receptors for pathogen-associated molecular patterns (PAMPs), such as Toll-like receptors (TLRs), which modulate their proinflammatory behavior. Derangements of the signals controlling these mechanisms are at the basis of the pathogenesis of different cholangiopathies, often extending beyond the classically recognized immune-mediated (primary biliary cirrhosis, primary sclerosing cholangitis), as in cystic fibrosis liver diseas