Man Y G, Ball W D, Marchetti L, Hand A R
Department of Anatomy, College of Medicine, Howard University, Washington, DC 20059, USA.
Anat Rec. 2001 Jun 1;263(2):202-14. doi: 10.1002/ar.1098.
The parenchyma of the submandibular gland in the adult male rat is self-renewing, with most newly formed acinar and granular duct cells believed to differentiate from the rapidly proliferating intercalated duct (ID) compartment. Since the ID cells are phenotypically diverse, based on their different expression of perinatal secretory proteins, we systemically injected tritiated thymidine for 24 hours, and followed the pattern of thymidine distribution in cells by autoradiography and immunocytochemistry of defined cellular phenotypes over a 1-month chase period. Proliferating cells were found within all parenchymal cell compartments; they were most numerous in ID, and primarily in those cells lacking immunoreactivity for the perinatal proteins SMG-B1, -C, and -D. The labeling index (LI) of the ID cells reached a peak at 7 days postinjection, and then decreased over the next 3 weeks. Concurrently, the LI increased significantly in those cells at the junctions of ID with both acini and granular ducts, and also within these larger parenchymal elements. We conclude that the ID cells not reactive for perinatal proteins proliferate to expand the ID compartment, and that ID cells at the ends of the ducts differentiate into both acinar and granular duct cells. Our data provide no evidence for the differentiation of ID cells into cells of striated ducts (SD); however, the small number of excretory duct (ED) profiles seen in our preparations showed extremely high LI (>25%), suggesting that more extensive data might reveal a precursor role for the ED in replacement of SD cells. In addition to the stepwise passage of cells from ID to other parenchymal elements at their junctions, the reported occurrence of occasional clusters of B1-positive acini (BAC) among the typical B1-negative acini had suggested an alternate pathway, in which entire segments of newly expanded ID might develop directly into a recapitulated perinatal stage of B1-reactive cell, pursuant to becoming mature acinar cells. Consistent with this suggestion, the BAC had a fourfold greater LI than typical adult acini; moreover, when analyzed by electron microscopic immunocytochemistry, they appeared similar to the novel perinatal Type III cells both ultrastructurally and in their pattern of B1-immunogold labeling. In contrast, the less common acini showing a sublingual gland phenotype had no significant difference in LI from typical acinar cells. Overall, our results emphasize the importance of the nonimmunoreactive ID cells in normal cellular replacement, and the possibility that ID can undergo en bloc differentiation into replacement acini as well as incremental addition of single cells at the boundaries of ID with acini and with granular ducts.
成年雄性大鼠下颌下腺的实质具有自我更新能力，大多数新形成的腺泡和颗粒导管细胞被认为是由快速增殖的闰管（ID）部分分化而来。由于ID细胞在表型上具有多样性，基于它们对围产期分泌蛋白的不同表达，我们系统地注射了氚标记的胸腺嘧啶核苷24小时，并在1个月的追踪期内通过放射自显影和特定细胞表型的免疫细胞化学方法追踪胸腺嘧啶核苷在细胞中的分布模式。在所有实质细胞部分都发现了增殖细胞；它们在ID中数量最多，主要存在于那些对围产期蛋白SMG - B1、- C和- D缺乏免疫反应性的细胞中。ID细胞的标记指数（LI）在注射后7天达到峰值，然后在接下来的3周内下降。同时，在ID与腺泡和颗粒导管交界处的细胞以及这些较大实质成分内的细胞中，LI显著增加。我们得出结论，对围产期蛋白无反应的ID细胞增殖以扩大ID部分，并且导管末端的ID细胞分化为腺泡和颗粒导管细胞。我们的数据没有提供ID细胞分化为纹状管（SD）细胞的证据；然而，在我们的制备物中看到的少量排泄管（ED）轮廓显示出极高的LI（>25%），这表明更广泛的数据可能揭示ED在替代SD细胞中的前体作用。除了细胞在ID与其交界处的其他实质成分之间逐步传递外，报道的在典型B1阴性腺泡中偶尔出现B1阳性腺泡簇（BAC）提示了另一种途径，即新扩张的ID的整个部分可能直接发展为B1反应性细胞的重现围产期阶段，随后成为成熟的腺泡细胞。与这一推测一致，BAC的LI比典型的成年腺泡大四倍；此外，通过电子显微镜免疫细胞化学分析时，它们在超微结构和B1免疫金标记模式上都与新的围产期III型细胞相似。相比之下，表现出舌下腺表型的不太常见的腺泡与典型腺泡细胞在LI上没有显著差异。总体而言，我们的结果强调了非免疫反应性ID细胞在正常细胞替代中的重要性，以及ID可能整体分化为替代腺泡以及在ID与腺泡和颗粒导管边界处逐个添加单个细胞的可能性。
