Purpose: Spinal cord injured patients are at increased risk for bladder carcinoma. Nitric oxide production in areas of chronic inflammation may provide a stimulus for carcinogenesis by serving as a source of nitrosating agents that generate potentially carcinogenic nitrosamines from secondary amines normally present in urine.
Materials and methods: To determine whether inducible nitric oxide synthase is expressed as a catalyst for sustained nitric oxide production by cellular elements in chronically inflamed bladder mucosa immunohistochemical studies were performed on mucosal biopsies obtained from 37 adults with spinal cord injury. All participants had required a chronic indwelling urethral or suprapubic catheter for greater than 8 years.
Results: Histopathological studies revealed active inflammatory infiltrates in all 37 biopsy specimens, squamous metaplasia in 20, epithelial dysplasia in 3 and carcinoma in 1. Inducible nitric oxide synthase was detected in inflammatory cells localized to the lamina propria. Inducible nitric oxide synthase positive cells were identified as macrophages using monoclonal antibodies to macrophage antigen. There was no inducible nitric oxide synthase expression in the urothelial cell layers. Immunostaining for inducible nitric oxide synthase was not detected in bladder mucosal biopsy specimens obtained from cadaveric organ donors.
Conclusions: Inducible nitric oxide synthase is expressed in inflammatory macrophages in areas of chronic inflammation in the bladder mucosa of spinal cord injured patients with a chronic indwelling bladder catheter. The expression of inducible nitric oxide synthase may potentially lead to the sustained production of nitric oxide and its oxidative products, the nitrosation of urinary amines and the formation of potentially carcinogenic nitrosamines in the bladder.