Metzger Roman, Schuster Tobias, Till Holger, Stehr Maximilian, Franke Folker-Ernst, Dietz Hans-Georg
Department of Pediatric Surgery, University of Munich, Germany.
J Urol. 2004 Aug;172(2):769-72. doi: 10.1097/01.ju.0000130571.15243.59.
Interstitial cells of Cajal (ICCs) have an important role in the regulation of gut motility as they are responsible for the slow wave activity of smooth muscle. It is still unknown if ICCs also occur in the human upper urinary tract. Since these cells express and are marked by the c-kit receptor CD117, we investigated its occurrence and distribution along the human upper urinary tract.
Tissues from 56 human ureters, spanning proximal, middle and distal ureter segments, were analyzed by indirect immunohistochemistry using the alkaline phosphatase-anti-alkaline phosphatase method and double labeling immunofluorescence on consecutive tissue sections. Several monoclonal and polyclonal antibodies to c-kit receptor were used in combination with various cell markers for histiocytic, mast cell, endothelial, epithelial, neuronal, smooth muscle and stem cell differentiation.
The c-kit receptor was found in 3 cell types of the ureter and in round or spindle-shaped cells. Due to their antigenic profile the first one was revealed as mast cells occurring in all layers of the ureteral wall except the urothelium. In contrast, the population of spindle-shaped cells was only marked by c-kit receptor, thus, resembling ICCs. These ICC-like cells were found among the inner and outer smooth muscle layers, and in the lamina propria. They showed a slight decrease from proximal to distal ureteral segments. However, unlike intestinal ICCs their cytomorphology differed and some cells, representing the third group of c-kit receptor positive cells, were found within the urothelium.
Our data demonstrate the presence of ICC-like cells and their ubiquitous distribution in the human ureter. The physiological importance and pathological significance of these findings must be evaluated by functional studies and investigations of certain pathological with urinary outflow disturbance conditions.
Cajal间质细胞(ICCs)在肠道运动调节中起重要作用,因为它们负责平滑肌的慢波活动。ICCs是否也存在于人类上尿路中仍不清楚。由于这些细胞表达c-kit受体CD117并以此为标记,我们研究了其在人类上尿路中的发生情况和分布。
使用碱性磷酸酶-抗碱性磷酸酶法间接免疫组织化学以及对连续组织切片进行双重标记免疫荧光,分析了来自56例人类输尿管的组织,这些输尿管跨越输尿管近端、中段和远端。几种针对c-kit受体的单克隆和多克隆抗体与用于组织细胞、肥大细胞、内皮细胞、上皮细胞、神经元、平滑肌和干细胞分化的各种细胞标记物联合使用。
在输尿管的3种细胞类型以及圆形或梭形细胞中发现了c-kit受体。根据其抗原谱,第一种被鉴定为肥大细胞,存在于输尿管壁除尿路上皮外的所有层中。相比之下,梭形细胞群体仅被c-kit受体标记,因此类似于ICCs。这些ICCs样细胞存在于内、外平滑肌层以及固有层中。从输尿管近端到远端节段,它们的数量略有减少。然而,与肠道ICCs不同,它们的细胞形态不同,并且在尿路上皮内发现了一些代表第三组c-kit受体阳性细胞的细胞。
我们的数据证明了ICCs样细胞在人类输尿管中的存在及其普遍分布。这些发现的生理重要性和病理意义必须通过功能研究以及对某些伴有尿流梗阻情况的病理学研究来评估。