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Effect of endothelin-1 on alpha-smooth muscle actin expression and on alveolar fibroblasts proliferation in interstitial lung diseases.

Endothelin-1 (ET-1) is a potent constrictor and mitogen peptide which is expressed in several pulmonary diseases. To elucidate the involvement of ET-1 in lung interstitial pathologic events, we assessed ET-1 secretion by alveolar macrophages (AM) and fibroblasts recovered from the bronchoalveolar la... Full description

Journal Title: International journal of immunopharmacology November 1999, Vol.21(11), pp.759-775
Main Author: Shahar, I
Other Authors: Fireman, E , Topilsky, M , Grief, J , Schwarz, Y , Kivity, S , Ben-Efraim, S , Spirer, Z
Format: Electronic Article Electronic Article
Language: English
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ID: ISSN: 0192-0561
Link: http://search.proquest.com/docview/69298744/?pq-origsite=primo
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title: Effect of endothelin-1 on alpha-smooth muscle actin expression and on alveolar fibroblasts proliferation in interstitial lung diseases.
format: Article
creator:
  • Shahar, I
  • Fireman, E
  • Topilsky, M
  • Grief, J
  • Schwarz, Y
  • Kivity, S
  • Ben-Efraim, S
  • Spirer, Z
subjects:
  • Actins–Metabolism
  • Adult–Cytology
  • Aged–Metabolism
  • Bronchoalveolar Lavage Fluid–Cytology
  • Cell Division–Metabolism
  • Cells, Cultured–Metabolism
  • Endothelin-1–Metabolism
  • Female–Metabolism
  • Fibroblasts–Physiopathology
  • Humans–Metabolism
  • Male–Physiopathology
  • Middle Aged–Physiopathology
  • Mitogens–Physiopathology
  • Muscle, Smooth–Physiopathology
  • Pulmonary Fibrosis–Physiopathology
  • Sarcoidosis–Physiopathology
  • Actins
  • Endothelin-1
  • Mitogens
ispartof: International journal of immunopharmacology, November 1999, Vol.21(11), pp.759-775
description: Endothelin-1 (ET-1) is a potent constrictor and mitogen peptide which is expressed in several pulmonary diseases. To elucidate the involvement of ET-1 in lung interstitial pathologic events, we assessed ET-1 secretion by alveolar macrophages (AM) and fibroblasts recovered from the bronchoalveolar lavage (BAL) of patients with idiopathic pulmonary fibrosis (IPF), sarcoidosis (SA) and from control subjects. We characterized in vitro alveolar fibroblasts of all subjects using monoclonal antibody specific to alpha -smooth muscle actin ( alpha -SM actin) and human fibroblast marker. We also examined the effect of ET-1 on the fibroblasts' mitogenesis and on their cytoskeletal phenotype. The AM recovered from IPF patients showed increased spontaneous secretion of ET-1 compared with cells from SA and control subjects. The expression of alpha -SM actin in the fibroblasts from IPF patients was significantly higher than in SA fibroblasts and normal lung fibroblasts. Assessing alveolar fibroblasts purity revealed a negative staining for alpha -SM actin in all SA and control fibroblasts, while alveolar fibroblasts recovered from IPF were 100% positive for alpha -SM actin, a reliable differentiation marker of myofibroblastic cells. Exposure of SA alveolar fibroblasts to ET-1 resulted in an increased expression of alpha -SM actin. Addition of exogenous ET-1 to alveolar fibroblasts culture stimulated DNA synthesis and proliferation in all groups. Moreover, neutralization of ET-1 by monoclonal antibody was shown to decrease super(3)H-thymidine incorporation in fibroblasts cultured with AM supernatants. These results suggest possible interactions between AM, myofibroblasts and fibroblasts in interstitial lung diseases (ILD). By modulating alpha -SM actin expression and exertion of the mitogenic effect on alveolar fibroblasts, ET-1 might play an important role in the fibrogenesis of ILD.
language: eng
source:
identifier: ISSN: 0192-0561
fulltext: fulltext
issn:
  • 01920561
  • 0192-0561
url: Link


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titleEffect of endothelin-1 on alpha-smooth muscle actin expression and on alveolar fibroblasts proliferation in interstitial lung diseases.
creatorShahar, I ; Fireman, E ; Topilsky, M ; Grief, J ; Schwarz, Y ; Kivity, S ; Ben-Efraim, S ; Spirer, Z
contributorShahar, I (correspondence author) ; Shahar, I (record owner)
ispartofInternational journal of immunopharmacology, November 1999, Vol.21(11), pp.759-775
identifierISSN: 0192-0561
subjectActins–Metabolism ; Adult–Cytology ; Aged–Metabolism ; Bronchoalveolar Lavage Fluid–Cytology ; Cell Division–Metabolism ; Cells, Cultured–Metabolism ; Endothelin-1–Metabolism ; Female–Metabolism ; Fibroblasts–Physiopathology ; Humans–Metabolism ; Male–Physiopathology ; Middle Aged–Physiopathology ; Mitogens–Physiopathology ; Muscle, Smooth–Physiopathology ; Pulmonary Fibrosis–Physiopathology ; Sarcoidosis–Physiopathology ; Actins ; Endothelin-1 ; Mitogens
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descriptionEndothelin-1 (ET-1) is a potent constrictor and mitogen peptide which is expressed in several pulmonary diseases. To elucidate the involvement of ET-1 in lung interstitial pathologic events, we assessed ET-1 secretion by alveolar macrophages (AM) and fibroblasts recovered from the bronchoalveolar lavage (BAL) of patients with idiopathic pulmonary fibrosis (IPF), sarcoidosis (SA) and from control subjects. We characterized in vitro alveolar fibroblasts of all subjects using monoclonal antibody specific to alpha -smooth muscle actin ( alpha -SM actin) and human fibroblast marker. We also examined the effect of ET-1 on the fibroblasts' mitogenesis and on their cytoskeletal phenotype. The AM recovered from IPF patients showed increased spontaneous secretion of ET-1 compared with cells from SA and control subjects. The expression of alpha -SM actin in the fibroblasts from IPF patients was significantly higher than in SA fibroblasts and normal lung fibroblasts. Assessing alveolar fibroblasts purity revealed a negative staining for alpha -SM actin in all SA and control fibroblasts, while alveolar fibroblasts recovered from IPF were 100% positive for alpha -SM actin, a reliable differentiation marker of myofibroblastic cells. Exposure of SA alveolar fibroblasts to ET-1 resulted in an increased expression of alpha -SM actin. Addition of exogenous ET-1 to alveolar fibroblasts culture stimulated DNA synthesis and proliferation in all groups. Moreover, neutralization of ET-1 by monoclonal antibody was shown to decrease super(3)H-thymidine incorporation in fibroblasts cultured with AM supernatants. These results suggest possible interactions between AM, myofibroblasts and fibroblasts in interstitial lung diseases (ILD). By modulating alpha -SM actin expression and exertion of the mitogenic effect on alveolar fibroblasts, ET-1 might play an important role in the fibrogenesis of ILD.
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titleEffect of endothelin-1 on alpha-smooth muscle actin expression and on alveolar fibroblasts proliferation in interstitial lung diseases.
authorShahar, I ; Fireman, E ; Topilsky, M ; Grief, J ; Schwarz, Y ; Kivity, S ; Ben-Efraim, S ; Spirer, Z
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