The Liver in the IgA Secretory Immune System. Dogs, But Not Rats and Rabbits, Are Suitable Models for Human Studies

Abstract

The liver transport of polymeric IgA (plgA) from plasma into bile and the immunohistochemical distribution of secretory component (SC) in the liver were studied in dogs, and compared to those in humans, rats, and rabbits. Results were as follows: (i) according to bile and serum protein concentrations and specific activities, plasma plgA in dogs, like in humans, is transported into bile cv∼10 times more efficiently than albumin, as compared to 320 and 1060 times in rabbits and rats, respectively, (ii) Only ∼1% of an i.v. dose of [125I]pIgA is transported into bile over 8 hr in dogs, like in humans, as compared to ∼50% over 3 hr in rats and rabbits. These results agree with much smaller daily fractional catabolic rates of intravascular plgA in dogs (0.28) and humans (0.48) than in rats (24.0). (iii) Total bile IgA contributes daily about 1.5 mg per kg to intestinal plgA in dogs, a figure similar in humans (0.8 mg per kg) but much smaller than in rats (38 mg per kg) and rabbits (35 mg per kg), (iv) Biliary obstruction in dogs, like in humans, results only in minor and late increases in serum plgA levels, contrasting with >8‐fold increases within 24 hr in rats and rabbits, (v) Unlike in rats and rabbits, SC in dog liver as well as in human liver cannot be detected in hepatocytes although clearly present in bile duct cells. To conclude: (i) major species differences in plasma‐to‐bile transport of plgA exist, most probably related to species differences in the ability of hepatocytes to synthetize SC. (ii) Bile duct cells, despite their membranous SC, are much less efficient than hepatocytes to transport plgA from plasma to bile, (iii) Dogs, but not rats and rabbits, provide a suitable experimental model for further studies on the relationships between the liver and the secretory IgA immune system in humans.