title: Elastase mediates the release of growth factors from lung in vivo.
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.
authors.affiliation: Department of Biochemistry and the Pulmonary Center at Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Jo Ann
authors.initials: JA
authors.lastname: Buczek-Thomas
authors.forename: Edgar C
authors.initials: EC
authors.lastname: Lucey
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Stone
authors.forename: Chia L
authors.initials: CL
authors.lastname: Chu
authors.forename: Celeste B
authors.initials: CB
authors.lastname: Rich
authors.forename: Isabel
authors.initials: I
authors.lastname: Carreras
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Goldstein
authors.forename: Judith A
authors.initials: JA
authors.lastname: Foster
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Nugent
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004549:Elastin / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000201:enzymology* / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D010196:Pancreatic Elastase / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D001798:Blood Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004549:Elastin; D010196:Pancreatic Elastase