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Translocation of Dimeric IgA through Neoplastic Colon Cells in Vitro¹

From the Department of Medicine, Division of Gastroenterology, of the Veterans Administration Medical Center and the University of Colorado Medical Center; and the Department of Pathology of the University of Colorado Medical Center, Denver, Colorado

Abstract

We studied the translocation of dimeric IgA across epithelium, using neoplastic human colon cells in culture as a source of epithelial cells, and immunoelectronmicroscopy with peroxidase-labeled antigens and antibodies. The cells had some of the ultrastructural characteristics of normal, mature epithelial cells, i.e., polarity, desmosomal junctions, and secretory component on their basal and lateral plasma membranes. Horseradish peroxidase-labeled dimeric IgA, exposed to the cells at 0°C, bound selectively to secretory component on the cell surfaces. At 37°C, the bound dimeric IgA was taken into the cells by endocytosis and transported apically through the cytoplasm in vesicles. After 30 min, IgA was discharged across the apical surface. Neither colchicine (10^-4 M) nor cytochalasin B (10^-5 M) interfered with binding or endocytosis of dimeric IgA, but colchicine inhibited intracellular transport of the IgA-containing vesicles.

These experiments demonstrated that dimeric IgA can be transported through living intestinal epithelial cells in vitro. The transport includes 1) specific binding of IgA dimers to secretory component on plasma membranes, 2) endocytosis of IgA in vesicles, 3) transcytoplasmic transport of the IgA-containing vesicles by a process involving microtubules, and 4) discharge of IgA at the apical surfaces.

Footnotes

¹ This study was supported in part by the Medical Research Service of the Veterans Administration; United States Public Health Service Grant CA-17342 from the National Cancer Institute through the National Large Bowel Cancer Project; United States Public Health Service Grants AI09109 and AM15663; and American Cancer Society Grant DT 14.

² Present address: Department of Pathology, Tokai University School of Medicine, Japan.

³ Address correspondence to: William R. Brown, M.D. (111E), Veterans Administration Medical Center, 1055 Clermont Street, Denver, Colorado 80220.

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