Cathepsin L activity and its inhibitor in human otitis media

Objective: We examined cathepsin L activity, expression of cystatin A, and copper- and zinc-containing superoxide dismutase in human chronic otitis me dia. The relationships of our findings to clinical findings (e.g., grade of bone destruction) were also studied. Design: Retrospective basic and clinical study. Setting: Department of Otolaryngology and First Department of Biochemistry, Kinki University School of Medicine, Osaka, Japan. Method: The human middle ear tissues evaluated in this study were surgicall y obtained from seven patients with cholesteatoma epithelium, three patient s with granulation tissues in cholesteatoma, three patients with granulatio n tissues in noncholesteatoma, and three patients with intact mucous membra ne of the middle ear. Main Outcome Measures: Cathepsin L activities in cholesteatoma epithelium, granulation tissues in cholesteatoma, or granulation tissues in noncholeste atoma were measured using Barrett's method. Cystatin A expressions were obs erved by Western blot analysis. Copper- and zinc-containing superoxide dism utase in cholesteatoma was examined immunohistochemically. Results: Mean cathepsin L activity was higher in diseased tissues than in i ntact mucous membranes of the middle ear. Granulation tissues with high cat hepsin L activity resulted in extensive bone destruction in both cholesteat omas and non-cholesteatomas of the middle ear. All cases with intact mucous membrane of the middle ear exhibited no expression of cystatin A. Seven of 10 cases with diseased tissues expressed cystatin A in cholesteatoma epith elium, granulation tissues in cholesteatoma, or granulation tissues in nonc holesteatoma. No relationships were found between cystatin A expression and grade of cathepsin L activity. Copper- and zinc-containing superoxide dism utase was more strongly positive in cholesteatoma epithelium regions than i n granulation tissues. Conclusion: These results suggest that copper- and zinc-containing superoxi de dismutase in cholesteatoma epithelium prevents complications by suppress ing cathepsin L activity.