Biochemical characterization and quantitation of the collagenous components of urethral stricture tissue

The collagenous composition of normal and strictured human urethral tissue was analyzed qualitatively by immunohistochemistry and quantitatively by 2-dimensional gel electrophoresis of cyanogen bromide digested tissue. Histological comparison of the normal and strictured urethral tissue showed that the normal urethral spongiosum was replaced by densely packed connective tissue fibers interspersed with fibroblasts in the strictured tissue. The immunohistochemical analysis of urethral tissue identified the presence of types I and III collagen fibers in normal spongiosum and in the connective tissue scar of strictured tissue. Estimation of the collagen type III:I ratio using scanning densitometry revealed a CB5:CB8 peptide ratio of 0.357 +/- 0.058 in the normal tissue, while the urethral stricture tissue had a CB5:CB8 ratio of 0.203 +/- 0.079 (p = 0.010). Total collagen content, as determined by hydroxyproline analysis, revealed no statistically significant differences between control and strictured tissue. Therefore, the normal urethral spongiosum was comprised of 75.1% type I collagen and 24.9% type III collagen. In contrast, the type I collagen in urethral stricture tissue was increased (83.9%), with a corresponding decrease in type III collagen (16.1%). This alteration in the ratio of collagen type III:I may explain the fibrotic noncompliant nature of urethral stricture scar tissue.