Histochemical studies on tissue plasminogen activator. Interrelationship between tissue plasminogen activator and alkaline phosphatase in the bladder wall

Abstract

The functional significances of the bladder epithelium are not yet well known. The transitional epithelium of the bladder is subjected to considerable physiological stimuli such as pressure changes during filling and emptying of the bladder and variations in the osmotic concentration of urine. The transitional epithelium of the bladder is well adapted to these stresses. It is generally known that the special histological structure and interrelationship of component cells of the transitional epithelium and the presence of a condensation of cytoplasm in surface cells are accepted generally. The mechanism by which the bladder epithelium is adapted to changes in the area of the mucous membrane during filling and emptying is also known. It has long been known experimentally and clinically that vesical mucosa regenerate rapidly even after its complete excision. The existence of the basal membrane in the bladder mucosa was demonstrated by many authors. Another open problems are that of active-transport function of the transitional epithelium.There have been numerous reports with regard to the histochemistry of the transitional epithelium. Many aUthors have described the localization of alkaline phosphatase in the bladder wall of various animal species, including frog, mouse, rat, guinea pig, rabbit, cat, dog and man. They described the presence of alkaline phosphatase in the inner cell layers of the epithelium but it was absent in the cells of the surface layer.Recently, attention has also been paid to the presence of extremely active tissue plasminogen activator in the bladder epithelium of many species. But detailed interrelationship between alkaline phosphatase and tissue plasminogen activator has not yet been well known.An attempt was made to contribute to the histophysiology of the transitional epithelium of the normal bladder by studying distribution of alkaline phosphatase and tissue plasminogen activator in the normal bladder wall of guinea pig. The localization of such substances on the bladder wall has not been studied previously.A total of 20 white adult guinea pigs, of both sexes, were used in the present study. The activity of plasminogen activator in the tissue and urine was examined by the modified histochemical fibrin slide technique. The distribution of alkaline phosphatase was demonstrated by a modification of the coupling azo dye method.The fibrinolytic activity of bladder urine varied slightly among different individuals, but the activity in the sediment and supernatant of urine did not appear after 90 minutes of incubation on the both plasminogen-rich or -free fibrin slide in all animals studied.In the normal bladder wall of guinea pig, fibrinolytic active-sites were observed at four different localizations as described below: (a) Fibrinolytic activity appeared diffusely widespread associated with the mucosa, originating from the transitional epithelium, after incubation periods ranging from 10 to 20 minutes. (b) Focal zones of lysis were seen in relation to some blood vessels in the submucosa and muscular coat after 20 to 30 minutes of incubation. (c) Lysed areas along some collection of desquamated epithelial cells were observed lying freely in the bladder cavity after 20 to 30 minutes of incubation. (d) Zones of lysis were found associated with the transitional epithelium and subepithelial connective tissue in the ureter which penetrate through the bladder wall.With regard to the distribution of alkaline phosphatase in the bladder, the reaction was intense in the thin layer of the subepithelial connective tissue located immediately below the lining basal membrane and apeared after shortest incubation periods (i. e. 5min.) than did the reaction in the transitional epithelium. The epithelium showed a moderately inte