Polymeric IgA Binding to the Human pIgR Elicits Intracellular Signalling, but Fails to Stimulate pIgR‐Transcytosis

• Published in: Scandinavian journal of immunology Vol. 53; no. 1; pp. 56 - 64
• Main Authors: Giffroy, D., Courtoy, P.‐J., Vaerman, J.‐P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-01-2001; Wiley Subscription Services, Inc
• Subjects: Adenocarcinoma - pathology; Animals; calcium; Calcium Signaling - drug effects; Cell Line - drug effects; DNA, Complementary - genetics; Dogs; Enzyme Activation - drug effects; Humans; Immunoglobulin A - genetics; Immunoglobulin A - immunology; Immunoglobulin A - metabolism; immunoglobulin receptors; Inositol 1,4,5-Trisphosphate - metabolism; Ionomycin - pharmacology; Ionophores - pharmacology; Kidney Tubules, Proximal - cytology; Lung Neoplasms - pathology; Protein Kinase C - drug effects; Protein Kinase C - physiology; Protein Transport - drug effects; Rabbits; Rats; Receptors, Polymeric Immunoglobulin - genetics; Receptors, Polymeric Immunoglobulin - metabolism; Receptors, Polymeric Immunoglobulin - physiology; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - metabolism; Second Messenger Systems - physiology; Signal Transduction - physiology; Species Specificity; Tetradecanoylphorbol Acetate - pharmacology; Transfection; Tumor Cells, Cultured; Vaccination
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1046/j.1365-3083.2001.00843.x

The intracellular pathway of polymeric immunoglobulin receptor (pIgR) is governed by multiple signals that lead to constitutive transcytosis. In addition, in transfected polarized MDCK cells, polymeric immunoglobulin A (pIgA) binding stimulates rabbit pIgR‐transcytosis, owing to phospholipase‐Cγ1 activation and increase of intracellular calcium. Transcytosis of rat pIgR across hepatocytes is similarly accelerated by pIgA injection. In contrast we show here that human Madrin‐Darby Canine Kidney (pIgR)‐transcytosis, in human Calu‐3 and human pIgR‐transfected MDCK cells, is not promoted by pIgA, as monitored by a continuous apical release of its secreted ectodomain. However, the incubation of cells expressing human or rabbit pIgR with pIgA induces a comparable IP3 production, and pIgR‐transcytosis of either species is accelerated by the protein kinase C (PKC)‐activator phorbol myristate acetate. Without pIgA, mimicking phospholipase‐C activation by combining low concentrations of phorbol myristate acetate with ionomycin, or high concentrations of ionomycin alone, stimulates the rabbit, but not the human, pIgR transcytosis. These data suggest that the species difference in pIgA‐induced pIgR‐transcytosis does not stem from the defective production of second messengers, but from a different sensitivity of pIgR to intracellular calcium. Our results outline the danger of extrapolating to humans the abundant data obtained from mucosal vaccination of laboratory animals.