Torihashi S, Ward S M, Nishikawa S, Nishi K, Kobayashi S, Sanders K M
Department of Physiology, University of Nevada School of Medicine, Reno 89557.
Cell Tissue Res. 1995 Apr;280(1):97-111. doi: 10.1007/BF00304515.
In vivo injection of a neutralizing, monoclonal antibody (ACK2) to the receptor tyrosine kinase (c-kit) disrupts the normal motility patterns of the mouse small intestine. Immunohistochemical studies showed that cells expressing c-kit-like immunoreactivity (c-kit-LI) decreased in numbers in response to ACK2, but the identity of these cells is unknown. We investigated the identity and development of the cells that express c-kit-LI in the mouse small intestine and colon. Cells in the region of the myenteric plexus and deep muscular plexus of the small intestine and in the subserosa, in the myenteric plexus region, within the circular and longitudinal muscle layers, and along the submucosal surface of the circular muscle in the colon were labeled with ACK2. The distribution of cells that express c-kit-LI was the same as that of interstitial cells (ICs). In whole-mount preparations cells with c-kit-LI were interconnected, forming a network similar to the network formed by cells that stained with methylene blue, which has been used as a marker for ICs in the mouse gastrointestinal tract. Immunocytochemistry verified that ICs were labeled with ACK2. Multiple injections of animals with ACK2 between days 0 and 8 post partum (pp) caused a dramatic reduction in the number of ICs compared to control animals. From an ultrastructural point of view, the proliferation and development appeared to be suppressed in some classes of ICs, while others displayed an altered course of development. Functional studies showed that the decrease in ICs was accompanied by a loss of electrical rhythmicity in the small intestine and reduced neural responses in the small bowel and colon. Morphological experiments showed that c-kit-positive cells are ICs, and physiological evidence reinforced the concept that ICs are involved in generation of rhythmicity and translation of neural inputs in gastrointestinal smooth muscles. Controlling the development of ICs provides a powerful new tool for the investigation of the physiological role of these cells.
向受体酪氨酸激酶（c-kit）体内注射一种中和性单克隆抗体（ACK2）会破坏小鼠小肠的正常运动模式。免疫组织化学研究表明，表达c-kit样免疫反应性（c-kit-LI）的细胞数量因ACK2而减少，但这些细胞的身份尚不清楚。我们研究了小鼠小肠和结肠中表达c-kit-LI的细胞的身份和发育情况。小肠肌间神经丛和深部肌丛区域以及结肠浆膜下、肌间神经丛区域、环形和纵行肌层内以及环形肌黏膜下表面的细胞都被ACK2标记。表达c-kit-LI的细胞分布与间质细胞（ICs）相同。在整装标本中，具有c-kit-LI的细胞相互连接，形成一个类似于用亚甲蓝染色的细胞所形成的网络，亚甲蓝已被用作小鼠胃肠道ICs的标志物。免疫细胞化学证实ICs被ACK2标记。在产后第0至8天（pp）多次给动物注射ACK2，与对照动物相比，ICs数量显著减少。从超微结构的角度来看，某些类型的ICs的增殖和发育似乎受到抑制，而其他ICs则显示出发育过程改变。功能研究表明，ICs的减少伴随着小肠电节律性的丧失以及小肠和结肠神经反应的减弱。形态学实验表明，c-kit阳性细胞是ICs，生理学证据强化了ICs参与胃肠道平滑肌节律性产生和神经输入转化的概念。控制ICs的发育为研究这些细胞的生理作用提供了一个强大的新工具。
