VECTORIAL TRANSCYTOSIS OF DIMERIC IGA BY THE CALU-3 HUMAN LUNG EPITHELIAL-CELL LINE - UP-REGULATION BY IFN-GAMMA

We have developed an in vitro airway epithelial cell model for dimeric immunoglobulin (Ig) A (dIgA) transcytosis that allows the assessment of polymeric Ig receptor (pIgR) gene expression and actual dIgA transp ort. Tight monolayers of human lung-derived Calu-3 adenocarcinoma cell s grown on permeable membranes expressed pIgR mRNA and released more s ecretory component (SC; P <0.01) and secretory IgA (sIgA; P <0.02) int o the apical medium than into the basolateral medium. Transcytosis of dIgA was not due to paracellular leakage and was inhibited to similar to 20 and 30% of control values by anti-pIgR antibodies and the compet itive ligand pentameric IgM, respectively. Interferon-gamma (IFN-gamma ; 200 U/ml) induced pIgR mRNA expression and increased apical release of free SC and sIgA in a dose-dependent fashion (P <0.0001). Basolater al addition of increasing amounts of dIgA dose dependently increased a pical sIgA release (P <0.0001). These data indicate that Calu-8 monola yers are capable of translocating dIgA through the pIgR. In addition, we show the integrated stimulatory effect of IFN-gamma on pIgR mRNA an d protein expression and dIgA transcytosis.