消化管平滑筋層の自動運動を調節する細胞群

我们对胃肠道肌层的两种细胞系进行了研究，得到以下结果：胃肠道肌层起搏器细胞肌层平滑肌细胞在肌层起搏器细胞的引导下发生自发的节律性收缩。人们已经认识到，起搏器细胞表达原癌基因c-kit，其发育依赖于c-kit信号通路。本研究发现，在新生小鼠腹部注射c-KIT中和抗体破坏c-KIT信号通路后，c-KIT阳性细胞不能发育为起搏器细胞，肌肉细胞自发收缩被破坏。c-KIT阳性细胞改变发育过程，开始表达平滑肌表型，向纵肌细胞分化。肌层巨噬细胞最近的研究表明，大量的常驻巨噬细胞位于肌肉层和浆膜下。电镜显示正常情况下无活性吞噬，功能未知。我们目前的研究证明了它们的功能之一，即它们在病理条件下调节平滑肌收缩。我们测量了平滑肌收缩力，并研究了内毒素脂多糖（LPS）孵育后巨噬细胞的行为。LPS孵育4-8小时后，巨噬细胞开始表达诱导型环氧合酶-2 （COX-2）和诱导型一氧化氮合酶（iNOS）。COX-2产生前列腺素（prostaglandins, pg），增强巨噬细胞iNOS的表达，促进NO的释放，影响肌肉层的机械活性。我们重点研究了胃肠道肌肉层的两类细胞，即起搏器细胞和肌肉巨噬细胞。我们证明了它们在肌肉层中的重要作用，但它们之间的相互作用是未来研究的主题。

We had inquired into two cell lines in the gastrointestinal muscle layer and obtained following results.1. Pacemaker cells of the gastrointestinal muscle layerSmooth muscle cells of the muscle layer have spontaneous rhythmical contractions conducted by pacemaker cells in the muscle layer. It has been realized that pacemaker cells express proto-oncogene c-kit and their development depends on c-KIT signal pathway. The present investigation realized that when c-KIT signal pathway impaired by injection of the neutralizing antibody for c-KIT into the abdomen of the newborn mouse, c-KIT positive cells failed to develop to pacemaker cells and then muscle cells disrupted spontaneous contractions. Further, c-KIT positive cells changed their developmental course, began to express smooth muscle phenotype and differentiated into longitudinal muscle cells.2. Muscularis macrophagesRecent investigations have demonstrated that a great number of resident macrophages are located in the muscle layer and at subserosa. Electronmicroscopy revealed inactive phagocytosis under the normal condition and their functions had been unknown. Our current investigation demonstrated one of their functions, that they modulated smooth muscle contraction under pathological conditions. We measured smooth muscle contractility and studied behavior of macrophages after incubation with endotoxin lipopolysaccharide (LPS). After 4-8 hours incubation with LPS, macrophages began to express inducible enzyme cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). COX-2 produced prostaglandins (PGs) which enhanced expression of iNOS in the macrophages and promoted release of NO, which affected the mechanical activity of the muscle layer.We focussed on two population of cell in the gastrointestinal muscle layer, i.e., pacemaker cells and muscular macrophages. We demonstrated their important roles in the muscle layer, however their interaction is the subject for a future study.