Loman S, Radl J, Jansen H M, Out T A, Lutter R
Department of Pulmonology, Academic Medical Center, University of Amsterdam, The Netherlands.
Am J Physiol. 1997 May;272(5 Pt 1):L951-8. doi: 10.1152/ajplung.1997.272.5.L951.
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.
我们开发了一种用于二聚体免疫球蛋白（Ig）A（dIgA）转胞吞作用的体外气道上皮细胞模型，该模型可用于评估聚合免疫球蛋白受体（pIgR）基因表达和实际的dIgA转运。在可渗透膜上生长的人肺来源的Calu-3腺癌细胞紧密单层表达pIgR mRNA，并且向顶端培养基中释放的分泌成分（SC；P <0.01）和分泌型IgA（sIgA；P <0.02）比向基底外侧培养基中更多。dIgA的转胞吞作用不是由于细胞旁渗漏引起的，并且分别被抗pIgR抗体和竞争性配体五聚体IgM抑制至对照值的约20％和30％。干扰素-γ（IFN-γ；200 U/ml）以剂量依赖性方式诱导pIgR mRNA表达并增加游离SC和sIgA的顶端释放（P <0.0001）。向基底外侧添加越来越多的dIgA剂量依赖性地增加顶端sIgA释放（P <0.0001）。这些数据表明Calu-3单层能够通过pIgR转运dIgA。此外，我们展示了IFN-γ对pIgR mRNA和蛋白表达以及dIgA转胞吞作用的综合刺激作用。
