Ninomiya H, Inui T, Masaki T
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
J Pharmacol Exp Ther. 1998 Jul;286(1):469-80.
Immunofluorescent analyses revealed distinct cellular/subcellular localization of endothelin (ET) receptors and ET-1 in the epithelial cell layer of guinea pig trachea. ETA was expressed predominantly in the basal cells. ETB was expressed predominantly in the ciliated columnar cells and was polarized at the apical side of the cell body within the cells. Anti-ET-1-immunoreactive cytoplasmic granules were contained in the secretory cells that were scattered throughout the epithelial layer. Cell proliferation assays with immersion cultures of differentially plated cells (basal cell-enriched, non-basal cell-enriched and mixed cell cultures) indicated the presence of paracrine ET-1 signaling pathways that transmit both positive and negative effects on the basal cell proliferation. Direct activation of ETA expressed on the basal cells caused enhancement of their growth, whereas that of ETB expressed on the ciliated columnar cells caused suppression of the basal cell growth. The latter effect was transmitted by nitric oxide whose production was stimulated by ETB activation. Furthermore, blockade of either ETA or ETB compromised the epithelial cell layer formation under the air-interphase culture, which indicates the dependence of tracheal epithelial remodeling on a balance between the positive and negative effects of ET-1 on the basal cell growth.
免疫荧光分析显示，内皮素（ET）受体和ET-1在豚鼠气管上皮细胞层中具有明显的细胞/亚细胞定位。ETA主要在基底细胞中表达。ETB主要在纤毛柱状细胞中表达，并在细胞体内的细胞顶端极化。抗ET-1免疫反应性细胞质颗粒存在于散布在上皮层中的分泌细胞中。对差异接种的细胞（富含基底细胞、非富含基底细胞和混合细胞培养物）进行浸没培养的细胞增殖试验表明，存在旁分泌ET-1信号通路，该通路对基底细胞增殖具有正负两种作用。直接激活基底细胞上表达的ETA会导致其生长增强，而激活纤毛柱状细胞上表达的ETB则会抑制基底细胞生长。后一种作用是由一氧化氮介导的，ETB激活会刺激一氧化氮的产生。此外，阻断ETA或ETB都会损害气-液界面培养下的上皮细胞层形成，这表明气管上皮重塑依赖于ET-1对基底细胞生长的正负作用之间的平衡。
