Danto S I, Shannon J M, Borok Z, Zabski S M, Crandall E D
Will Rogers Institute Pulmonary Research Center, University of Southern California, Los Angeles 90033, USA.
Am J Respir Cell Mol Biol. 1995 May;12(5):497-502. doi: 10.1165/ajrcmb.12.5.7742013.
Alveolar epithelial type II (AT2) cells have been thought to be the progenitors of terminally differentiated type I (AT1) cells in the adult animal in vivo. In this study, we used an AT1 cell-specific monoclonal antibody (mAb VIII B2) to investigate expression of the AT1 cell phenotype accompanying reversible changes in expression of the AT2 cell phenotype. AT2 cells were isolated and cultured either on attached collagen gels or on gels detached 1 or 4 days after plating and maintained thereafter as floating gels. Monolayers on both attached and floating gels were harvested on days 4 and 8 and analyzed by electron microscopy for changes in morphology and binding of mAb VIII B2. Results indicate that: (1) alveolar epithelial cells (AEC) on attached gels develop characteristics of the AT1 cell phenotype, (2) AEC on gels detached on day 1 maintain features of the AT2 cell phenotype (and do not react with mAb VIII B2), and (3) the expression of AT1 cell phenotypic traits seen by day 4 on attached gels is reversed after detachment. We conclude that commitment to the AT1 and AT2 cell lineages requires continuous regulatory input to maintain the differentiated states, and that transdifferentiation between AT2 and AT1 cells may be reversible.
在成年动物体内，肺泡II型上皮（AT2）细胞一直被认为是终末分化的I型（AT1）细胞的祖细胞。在本研究中，我们使用一种AT1细胞特异性单克隆抗体（mAb VIII B2）来研究伴随AT2细胞表型表达可逆变化的AT1细胞表型的表达情况。将AT2细胞分离出来，接种在附着的胶原凝胶上，或者在接种后1天或4天分离凝胶，并在此后作为漂浮凝胶进行培养。在第4天和第8天收获附着和漂浮凝胶上的单层细胞，通过电子显微镜分析其形态变化以及mAb VIII B2的结合情况。结果表明：（1）附着凝胶上的肺泡上皮细胞（AEC）呈现出AT1细胞表型的特征；（2）第1天分离凝胶上的AEC保持AT2细胞表型的特征（且不与mAb VIII B2反应）；（3）附着凝胶上第4天出现的AT1细胞表型特征在凝胶分离后发生逆转。我们得出结论，向AT1和AT2细胞谱系的分化需要持续的调节输入以维持分化状态，并且AT2和AT1细胞之间的转分化可能是可逆的。
