Apoptotic Activity is Increased in the Newly Formed Fibromyxoid Connective Tissue in Bronchiolitis Obliterans Organizing Pneumonia

Abstract.

Bronchiolitis obliterans organizing pneumonia (BOOP) and usual interstitial pneumonia (UIP) are clinically and histologically distinguishable interstitial lung diseases both sharing the presence of the newly formed fibromyxoid connective tissue as a histologic feature. In BOOP the newly formed connective tissue is susceptible to even complete reversal, but in UIP it participates in the remodeling of the pulmonary tissue. In this study we have tested the hypothesis that the apoptotic activity in the fibromyxoid lesions is higher in BOOP than in UIP. Apoptotic activity in cells of the newly formed connective tissue in BOOP and UIP was visualized by TUNEL. Apoptosis-regulating proteins bcl-2, mcl-1, and bax were visualized by immunohistochemistry. The number of the apoptotic events was given as an apoptotic index giving the percentage of the apoptotic cells and bodies of the total cell number. Our results show that the apoptotic activity is clearly higher in the fibromyxoid lesions of BOOP (mean, 0.7; S.D., ±0.51) compared with those of UIP (mean, 0.13; S.D., ±0.14, p < 0.003). The results thus suggest that apoptosis has an important role in the resolution process of the newly formed connective tissue in BOOP. The low level of apoptosis in UIP could, on the other hand, suggest that a decreased apoptosis in cells of the fibromyxoid stroma might pathogenetically relate to a decreased resolution of these lesions in UIP. No significant difference was found in the expression of bcl-2, mcl-1, and bax in BOOP and in UIP, suggesting that regulation of apoptosis might partly bypass the influence of these proteins.