Hepatocyte handling of immunoglobulin A in the rat: the role of microtubules.
Plasma-derived dimeric immunoglobulin A is transported through liver parenchymal cells into bile, in association with its glycoprotein receptor secretory component, by a vesicular transport system. This study was designed to determine the effects of colchicine, a microtubule-disrupting agent, and thus the role of microtubules on the uptake, intracellular transport, and subsequent biliary secretion of dimeric immunoglobulin A. In vivo studies in rats showed that colchicine treatment reduced the amount of intraportally injected 125I-dimeric immunoglobulin A that appeared in the bile. It was also found that although the livers in colchicine-treated animals could sequester and internalize immunoglobulin A, it was not readily secreted into bile. In vitro studies using peroxidase-labeled antisecretory component and 125I-dimeric immunoglobulin A autoradiography were both used to determine the site of this block in immunoglobulin A secretion. These studies demonstrate that colchicine disruption of microtubules (a) has little initial effect on the binding and internalization of dimeric immunoglobulin A; (b) has a major effect on the translocation of immunoglobulin A-containing vesicles within the hepatocyte, and (c) most likely prevents the translocation of newly synthesized secretory component to the plasma membrane.
D000818:Animals; D001345:Autoradiography; D001692:Biological Transport; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007457:Iodine Radioisotopes; D008099:Liver / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D012635:Secretory Component
D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007457:Iodine Radioisotopes; D012635:Secretory Component; D003078:Colchicine