Functional differences between hepatocytes and biliary epithelial cells in handling polymeric immunoglobulin A2 in humans, rats, and guinea pigs

Abstract

Immunoglobulin A (IgA) in bile plays an important role in preventing the biliary tract from infection. In the present study, to clarify the functional differences between hepatocytes and biliary epithelial cells (BEC) in handling polymeric IgA2 (pIgA2), the major and important IgA in bile, we have determined in different species the binding characteristics of 125I-labeled pIgA2 to tissue sections of human, rat, and guinea pig livers. We have also examined the binding and transport features of 125I-labeled and gold-labeled pIgA2 in cultured hepatocytes and cultured BEC of rat and guinea pig. Asialofetuin, an asialoglycoprotein, or an antisecretory component antibody was used for determining the binding characteristics of pIgA2 to the cells. Grains of 125I-pIgA2 were morphometrically analyzed. In tissue sections, 125I-pIgA2 was predominantly bound to rat hepatocytes as well as to human and guinea pig BEC. The binding of 125I-pIgA2 to the cells was significantly inhibited by pretreatment with an antisecretory component (SC) antibody (P < .001), but not by preloaded asialofetuin. In cultured cells, labeled pIgA2 was observed binding predominantly to rat hepatocytes and guinea pig BEC as compared with rat BEC and guinea pig hepatocytes (both P < .001), respectively, and gold particles of gold-labeled pIgA2 were localized in the tubulovesicular structures and biliary luminal spaces of those cells. These results suggested that pIgA2 was bound selectively to hepatocytes in the rat liver, and to BEC in the human and guinea pig livers, through the SC but not through an asialoglycoprotein receptor, and was transported transcellularly and secreted into bile.

Tumor necrosis factor‐α and interferon‐γ directly impair epithelial barrier function in cultured mouse cholangiocytes

“…For F‐actin‐staining, cells were fixed with 1% formaldehyde in PBS and permeabilized with 0.2% Triton‐X 100 in PBS followed by incubation with rhodarnine– phalloidin. A confocal laser scanning microscope (LSM‐GB200; Olympus, Tokyo, Japan) equipped with an Argon/Krypton laser capable of dual excitation and detection was used in order to visualize the distribution of immunostaining for these proteins and F‐actin (32).…”

The immunobiology of cholangiocytes

“…In some animals (rats, mice and rabbits), the secretory component is synthesized and expressed on the sinusoidal surface of the hepatocytes and sIgA is transported to bile canaliculi through hepatocytes. In other animals (dog, guinea and sheep), as well as in humans, the secretory component is not expressed in hepatocytes, instead, it is a process associated with cholangiocytes 79 …”

“…In other animals (dog, guinea and sheep), as well as in humans, the secretory component is not expressed in hepatocytes, instead, it is a process associated with cholangiocytes. 79 Transport of sIgA through cholangiocytes into bile is an important component of biliary mucosal immunity in humans. 12 IgAs could be a protective factor for bile ducts by preventing the attachment of pathogens or their toxins to the surface of cholangiocytes.…”

The immunobiology of bile and biliary epithelium

“…As discussed above, it is known that IgA is transported through the BEC into the bile by binding to the secretory component in the basal part of the BEC. 16 Antimitochondrial IgA could be involved in the injury of BEC in PBC by binding PDC-2 inside the BEC. In fact, it has been shown that during the intracellular transport from periductal tissue into the bile duct lumen, IgA AMA colocalizes with mitochondria in Madine Darby canine kidney cells.…”