PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Richard J Lang; Mary A Tonta; Beata Z Zoltkowski; William F Meeker; Igor Wendt; Helena C Parkington Journal: J Physiol Date: 2006-08-31 Impact factor: 5.182