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Published ahead of print on June 10, 2004, doi:10.1165/rcmb.2003-0420OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 31, pp. 344-350, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2003-0420OC

Elastase Mediates the Release of Growth Factors from Lung In Vivo

Jo Ann Buczek-Thomas, Edgar C. Lucey, Phillip J. Stone, Chia L. Chu, Celeste B. Rich, Isabel Carreras, Ronald H. Goldstein, Judith A. Foster and Matthew A. Nugent

Department of Biochemistry and the Pulmonary Center at Boston University School of Medicine, and the VA Boston Healthcare System, Boston, Massachusetts

Address correspondence to: Matthew A. Nugent, Ph.D., Department of Biochemistry, K420, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118. E-mail: nugent{at}biochem.bumc.bu.edu

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-ß (TGF-ß), after intratracheal instillation of porcine pancreatic elastase into mice. We found that elastase promoted a time-dependent release of FGF-2 and TGF-ß1 from the lung into bronchoalveolar lavage (BAL) fluid. A large fraction of the TGF-ß1 in BAL fluid was in the active form (~ 60%), suggesting that elastase might participate in the activation of TGF-ß1 from its latent form. Analysis of the levels of FGF-2 and TGF-ß1 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-ß1, suggesting that the TGF-ß1 in BAL fluid could have come from lung cells/matrix. Additional in vitro studies also indicated that TGF-ß1 plays a role in upregulating elastin mRNA levels. These data suggest that elastase releases growth factors from lung that participate in elastolytic injury responses.

Abbreviations: bronchoalveolar lavage, BAL • bovine serum albumin, BSA • chronic obstructive pulmonary disease, COPD • diisopropyl fluorophosphate, DFP • extracellular matrix, ECM • enzyme-linked immunosorbent assay, ELISA • fibroblast growth factor, FGF • glycosaminoglycan, GAG • heparan sulfate proteoglycan, HSPG • phosphate-buffered saline, PBS • porcine pancreatic elastase, PPE • transforming growth factor-ß, TGF-ß




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