Elastase Mediates the Release of Growth Factors from Lung In Vivo

• Published in: American journal of respiratory cell and molecular biology Vol. 31; no. 3; pp. 344 - 350
• Main Authors: Buczek-Thomas, Jo Ann, Lucey, Edgar C, Stone, Phillip J, Chu, Chia L, Rich, Celeste B, Carreras, Isabel, Goldstein, Ronald H, Foster, Judith A, Nugent, Matthew A
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01-09-2004; American Thoracic Society
• Subjects: Animals; Blood Proteins - metabolism; Cells, Cultured; Elastin - biosynthesis; Elastin - genetics; Female; Fibroblast Growth Factor 2 - drug effects; Fibroblast Growth Factor 2 - metabolism; Fibroblast Growth Factor 2 - secretion; Fibroblasts - drug effects; Fibroblasts - metabolism; Lung - enzymology; Lung - physiopathology; Lung - secretion; Mice; Pancreatic Elastase - metabolism; Pancreatic Elastase - pharmacology; Rats; Reaction Time - drug effects; Reaction Time - physiology; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Transforming Growth Factor beta - drug effects; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - secretion; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2003-0420OC

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.