消化管平滑筋層の自動運動を調節する細胞群

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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.