Huling S, Fournier G R, Feren A, Chuntharapai A, Jones A L
Department of Medicine, University of California, San Francisco 94121.
Proc Natl Acad Sci U S A. 1992 May 15;89(10):4260-4. doi: 10.1073/pnas.89.10.4260.
In the rat, secretion of polymeric IgA from serum into bile is dependent upon the presence of a functional polymeric immunoglobulin receptor (pIgR) that acts as a hepatocyte plasma membrane receptor for ligand binding and as a transcellular transport molecule. The objective of this study was to document the developmental maturation and regulation of functionally intact rat liver pIgR. An adult pattern of IgA secretion was not detected until after day 23 postpartum (dPP), by using intravenously injected 125I-labeled dimeric IgA. Radioactive dimeric IgA was not detectable in hepatocyte transport vesicles until 21 dPP by electron microscopy autoradiographic analysis. By using a rabbit polyclonal antibody against the rat secretory component domain of the pIgR, Western blot analysis demonstrated that the plasma-membrane-bound pIgR levels in hepatocytes from rats aged 19-22 dPP increased 10-fold during this period. To determine whether or not this increase in membrane-bound pIgR reflected increased pIgR gene expression, we probed Northern blots of total cellular RNA extracted from neonatal rat liver with pIgR cDNA [GORF-1; Banting, G., Brake, B., Braghetta, P., Luzio, J.P. & Stanley, K. K. (1989) FEBS Lett. 254, 177-183]. The pIgR RNA levels between 19 and 22 dPP rose more than 20-fold and paralleled the increased membrane-bound pIgR protein during this same interval. These data demonstrate a developmentally regulated process that controls the ontogeny of biliary dimeric IgA secretion at the termination of the third week postpartum. The process appears to depend on the up-regulation of pIgR gene expression.
在大鼠中，血清中的聚合型IgA向胆汁中的分泌依赖于功能性聚合免疫球蛋白受体（pIgR）的存在，该受体作为肝细胞质膜受体用于配体结合，并作为跨细胞转运分子。本研究的目的是记录功能完整的大鼠肝脏pIgR的发育成熟和调节情况。通过静脉注射125I标记的二聚体IgA，直到产后第23天（dPP）后才检测到成年模式的IgA分泌。通过电子显微镜放射自显影分析，直到21 dPP才能在肝细胞转运小泡中检测到放射性二聚体IgA。使用针对pIgR大鼠分泌成分结构域的兔多克隆抗体，蛋白质印迹分析表明，在此期间，19 - 22 dPP大鼠肝细胞中与质膜结合的pIgR水平增加了10倍。为了确定膜结合pIgR的这种增加是否反映了pIgR基因表达的增加，我们用pIgR cDNA [GORF-1；班廷，G.，布雷克，B.，布拉盖塔，P.，卢齐奥，J.P. & 斯坦利，K.K.（1989年）《欧洲生物化学学会联合会快报》254，177 - 183]探测从新生大鼠肝脏提取的总细胞RNA的Northern印迹。在19至22 dPP之间，pIgR RNA水平上升了20多倍，并且在同一时间段内与膜结合pIgR蛋白的增加平行。这些数据证明了一个发育调节过程，该过程在产后第三周结束时控制胆汁中二聚体IgA分泌的个体发生。这个过程似乎依赖于pIgR基因表达的上调。
