| Angiogenesis, apoptosis and re-epithelialization at the foci of recent injury in usual interstitial pneumonia and bronchiolitis obliterans organizing pneumonia | ||
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The present study addressed the role of angiogenesis, apoptosis and re-epithelialization in the pathogenesis of pulmonary fibrosis. In the newly formed intraluminal connective tissue of BOOP, there was wide and early capillarization often resembling granulation tissue formation. Capillarization paralleled with the immunohistochemical localization of VEGF, Flk-1, Flt-1 and bFGF. Apoptotic activity was increased within the newly formed connective tissue obviously contributing to the reduced cellularity of the intraluminal connective tissue in BOOP. There was also regular re-epithelialization of the newly formed intraluminal connective tissue with orderly layered and morphologically uniform regenerating pneumocytes, synthesizing laminin-5 γ 2 chain.
In UIP the capillarization was sparse within the newly formed intraluminal connective tissue, but pronounced in the areas of mural incorporating fibrosis, showing delayed capillarization at the primary site of the injury. Also, the apoptotic activity of the newly formed intraluminal connective tissue was lower in UIP than in BOOP, and the apoptotic activity can even be lower than in normal lung interstitium. Despite the synthesis of laminin-5 γ 2 chain, the re-epithelialization seems to be disturbed or delayed in UIP. The extent of re-epithelialization of the newly formed connective tissue was lower in UIP when compared to BOOP, and there was both morphological and structural abnormality of regenerating epithelial cells in UIP.
Based on these findings it seems evident that in BOOP, an efficient repair process takes place after lung injury, while in UIP, the repair process is disturbed or delayed. Thus, the results of the present study support the new concept of abnormal healing of lung injury as an important part of the pathogenesis of UIP. However, the pathogenesis of pulmonary fibrosis is most complex with multiple interactions between different cell types and signaling molecules, and more knowledge is needed about pathogenetic factors leading to the exaggerated fibroproliferative response in UIP. Understanding the pathogenesis of pulmonary fibrosis is essential for the development of new therapeutic strategies against UIP.