Elastase Mediates the Release of Growth Factors from Lung <i>In Vivo</i>

Abstract

Uncontrolled elastase activity is involved in the development of several types of lung disease. Previous reports demonstrated that growth factors are liberated from pulmonary matrix storage sites by elastase; however, release of these entities in vivo is not well defined. In the present study, we investigated the release of fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-beta), after intratracheal instillation of porcine pancreatic elastase into mice. We found that elastase promoted a time-dependent release of FGF-2 and TGF-beta1 from the lung into bronchoalveolar lavage (BAL) fluid. A large fraction of the TGF-beta1 in BAL fluid was in the active form (approximately 60%), suggesting that elastase might participate in the activation of TGF-beta1 from its latent form. Analysis of the levels of FGF-2 and TGF-beta1 in mouse blood indicated that the growth factors in BAL fluid were not entirely derived from blood. Moreover, elastase treatment of pulmonary fibroblasts cultures caused the release of TGF-beta1, suggesting that the TGF-beta1 in BAL fluid could have come from lung cells/matrix. Additional in vitro studies also indicated that TGF-beta1 plays a role in upregulating elastin mRNA levels. These data suggest that elastase releases growth factors from lung that participate in elastolytic injury responses.