Bronchoalveolar lavage fluid from immature rats with hyperoxia-induced airway remodeling is mitogenic for airway smooth muscle.

E. T. Naureckas*, M. B. Hershenson, M. K. Abe, M. D. Kelleher, C. Florio, S. I. Heisler, M. Absher, J. N. Evans, R. W. Samsel, J. Solway

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

We previously demonstrated that hyperoxia-exposed immature rats develop airway smooth muscle layer thickening; this remodeling appears partially attributable to smooth muscle hyperplasia. In this study, we tested the hypothesis that excess mitogenic activity for airway smooth muscle cells is present within the lungs of hyperoxia-exposed immature rats. We assessed the proliferative effect of bronchoalveolar lavage (BAL) fluid from air- and O2-exposed animals on cultured rat tracheal smooth muscle cells. BAL fluids from air- or O2-exposed immature rats increased DNA synthesis ([3H]-thymidine incorporation at 24 h of incubation) and cell number (compared with DMEM-treated control cells, at 2 days of incubation), but BAL fluid from O2-exposed animals had significantly greater mitogenic effects. This excess mitogenic activity was lipid inextractable and was ablated by trypsin digestion, indicating that at least one polypeptide growth factor was responsible; molecular sieve fractionation demonstrated a molecular weight of > 10 kD. Because platelet-derived growth factor (PDGF) has been identified in other models of hyperoxia exposure, we tested the further hypothesis that PDGF contributes to the observed excess mitogenic activity. Addition of neutralizing anti-PDGF antibodies to BAL-stimulated smooth muscle cultures did not reduce BAL fluid-induced mitogenesis. These data indicate that the lungs of O2-exposed rats contain excess mitogenic activity for airway smooth muscle, attributable to non-PDGF polypeptide growth factors. It is conceivable that this abnormal mitogenic activity contributes to O2-induced airway smooth muscle remodeling observed in immature rats in vivo.

Original languageEnglish (US)
Pages (from-to)268-274
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume12
Issue number3
DOIs
StatePublished - Mar 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Naureckas, E. T., Hershenson, M. B., Abe, M. K., Kelleher, M. D., Florio, C., Heisler, S. I., Absher, M., Evans, J. N., Samsel, R. W., & Solway, J. (1995). Bronchoalveolar lavage fluid from immature rats with hyperoxia-induced airway remodeling is mitogenic for airway smooth muscle. American journal of respiratory cell and molecular biology, 12(3), 268-274. https://doi.org/10.1165/ajrcmb.12.3.7873192