Polymeric IgA binding to the human pIgR elicits intracellular signalling, but fails to stimulate pIgR-transcytosis.
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-C gamma 1 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.
Giffroy
D
D
Experimental Medicine, Université catholique de Louvain and Christian de Duve Institute of Cell Pathology, B-1200 Brussels, Belgium.
Courtoy
P J
PJ
Vaerman
J P
JP
D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology; D008175:Lung Neoplasms / Q000473:pathology; D011493:Protein Kinase C / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013045:Species Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014611:Vaccination
D018076:DNA, Complementary; D007070:Immunoglobulin A; D007476:Ionophores; D019056:Receptors, Polymeric Immunoglobulin; D011993:Recombinant Fusion Proteins; C034639:polymeric IgA; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate