Published ahead of print on June 10, 2004, doi:10.1165/rcmb.2003-0420OC
Am. J. Respir. Cell Mol. Biol., Volume 31, Number 3, September 2004, 344-350
A more recent version of this article appeared on September 1, 2004
Submitted on November 20, 2003
Revised on June 8, 2004
Elastase Mediates the Release of Growth Factors from Lung In Vivo
Jo Ann Buczek-Thomas1, Edgar C Lucey2, Phillip J Stone1, Chia L Chu1, Celeste B Rich1, Isabel Carreras1, Ronald H Goldstein2, Judith A Foster1, and Matthew A Nugent1*
1 Department of Biochemistry and Pulmonary Center, Boston University School of Medicine, Boston, MA, USA,
2 VA Boston Healthcare System, Boston, MA, USA
* To whom correspondence should be addressed. 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-beta (TGF- ), following intratracheal instillation of porcine pancreatic elastase into mice. We found that elastase promoted a time dependent release of FGF-2 and TGF- 1 from the lung into bronchoalveolar lavage (BAL) fluid. A large fraction of the TGF 1 in BAL fluid was in the active form (~60%), suggesting that elastase might participate in the activation of TGF- 1 from its latent form. Analysis of the levels of FGF-2 and TGF- 1 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- 1, suggesting that the TGF- 1 in BAL fluid could have come from lung cells/matrix. Additional in vitro studies also indicated that TGF- 1 plays a role in upregulating elastin mRNA levels. These data suggest that elastase releases growth factors from lung that participate in elastolytic injury responses.
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