Torihashi S, Nishi K, Tokutomi Y, Nishi T, Ward S, Sanders K M
Department of Anatomy, Nagoya University School of Medicine, Tsurumai, Nagoya, Japan.
Gastroenterology. 1999 Jul;117(1):140-8. doi: 10.1016/s0016-5085(99)70560-3.
BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) serve as pacemaker cells and mediators of neurotransmission from the enteric nervous system to gastrointestinal muscles. ICC develop from mesenchymal cells that express c-Kit, and signaling via Kit receptors is necessary for normal development of ICC. We studied the fate of functionally developed ICC after blockade of Kit receptors to determine whether ICC undergo cell death or whether the phenotype of the cells is modified. The fate of undeveloped ICC was also investigated.
Neutralizing, anti-Kit monoclonal antibody (ACK2) was administered to mice for 8 days after birth. ICC in the small intestine were examined by immunohistochemistry and electron microscopy. Occurrence of apoptosis was also assayed.
When Kit receptors were blocked, ICC nearly disappeared from the small intestine. Apoptosis was not detected in regions where ICC are normally distributed. Remaining Kit-immunopositive cells in the pacemaker region of the small intestine developed ultrastructural features similar to smooth muscle cells, including prominent filament bundles and expression of the muscle-specific intermediate filament protein, desmin, and smooth muscle myosin. ICC of the deep muscular plexus normally develop after birth in the mouse. Precursors of these cells remained in an undifferentiated state when Kit was blocked.
These data, along with previous studies showing that ICC in the pacemaker region of the small intestine and longitudinal muscle cells develop from the same Kit-immunopositive precursor cells, suggest inherent plasticity between the ICC and smooth muscle cells that is regulated by Kit-dependent cell signaling.
Cajal间质细胞（ICC）作为起搏细胞以及从肠神经系统到胃肠肌肉的神经传递介质。ICC由表达c-Kit的间充质细胞发育而来，通过Kit受体的信号传导对于ICC的正常发育是必需的。我们研究了Kit受体被阻断后功能已发育的ICC的命运，以确定ICC是否经历细胞死亡或细胞表型是否被改变。未发育的ICC的命运也进行了研究。
出生后8天给小鼠注射中和性抗Kit单克隆抗体（ACK2）。通过免疫组织化学和电子显微镜检查小肠中的ICC。还检测了细胞凋亡的发生情况。
当Kit受体被阻断时，ICC几乎从小肠中消失。在ICC正常分布的区域未检测到细胞凋亡。小肠起搏区域中剩余的Kit免疫阳性细胞呈现出与平滑肌细胞相似的超微结构特征，包括明显的细丝束以及肌肉特异性中间丝蛋白结蛋白和平滑肌肌球蛋白的表达。小鼠深层肌丛的ICC通常在出生后发育。当Kit被阻断时，这些细胞的前体保持未分化状态。
这些数据，连同先前的研究表明小肠起搏区域的ICC和纵行肌细胞由相同的Kit免疫阳性前体细胞发育而来，提示ICC和平滑肌细胞之间存在由Kit依赖性细胞信号传导调节的内在可塑性。
