Vectorial transcytosis of dimeric IgA by the Calu-3 human lung epithelial cell line: upregulation 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 transport. Tight monolayers of human lung-derived Calu-3 adenocarcinoma cells grown on permeable membranes expressed pIgR mRNA and released more secretory component (SC; P < 0.01) and secretory IgA (sIgA; P < 0.02) into the apical medium than into the basolateral medium. Transcytosis of dIgA was not due to paracellular leakage and was inhibited to approximately 20 and 30% of control values by anti-pIgR antibodies and the competitive 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). Basolateral addition of increasing amounts of dIgA dose dependently increased apical sIgA release (P < 0.0001). These data indicate that Calu-3 monolayers are capable of translocating dIgA through the pIgR. In addition, we show the integrated stimulatory effect of IFN-gamma on pIgR mRNA and protein expression and dIgA transcytosis.
Loman
S
S
Department of Pulmonology, Academic Medical Center, University of Amsterdam, The Netherlands.
Radl
J
J
Jansen
H M
HM
Out
T A
TA
Lutter
R
R
D000906:Antibodies / Q000276:immunology; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D011108:Polymers; D012333:RNA, Messenger / Q000378:metabolism; D019056:Receptors, Polymeric Immunoglobulin / Q000276:immunology; D012635:Secretory Component / Q000235:genetics
D000906:Antibodies; D007070:Immunoglobulin A; D011108:Polymers; D012333:RNA, Messenger; D019056:Receptors, Polymeric Immunoglobulin; D012635:Secretory Component; D007371:Interferon-gamma