Elastase-induced lung emphysema in rats is not reduced by hematopoietic growth factors when applied preventionally

Virchows Arch. 2008 Jun;452(6):675-88. doi: 10.1007/s00428-008-0591-z. Epub 2008 Apr 25.

Abstract

We hypothesized that formation of pulmonary emphysema could be diminished after previous activation of stem cells. Animals received either a daily dose of the hematopoietic growth factors (GF; recombinant rat stem cell factor plus recombinant granulocyte colony stimulating factor; n=6, Elastase/GF group) or vehicle (n=9, Elastase/Sham group) starting 3 days before intratracheal instillation of elastase or vehicle and continued for another 25 days. Control animals were treated with NaCl (n=9, Sham/Sham group). On day 25, in all animals, a 2-mL pump was implanted subcutaneously that delivered 200 microg/h 5-bromo-2-desoxyuridine (BrdU) until study termination. Compared to controls, the Elastase/Sham group exhibited elevated total lung capacity (TLC) and functional residual capacity (FRC), significantly increased mean free alveolar pathway, alveolar volume, and decreased septal density. The Elastase/GF group showed (1) a significant increase of TLC and FRC, (2) a significant increase in alveolar size and volume, (3) a significant reduction of septal density, volume, and thickness. Proliferation in lung parenchyma and in terminal bronchioles remained significantly decreased in the Elastase/Sham group and the Elastase/GF group. Blood cell number has significantly increased in the Elastase/GF group. The application of GF-enhanced pulmonary emphysema, presumable because of increased inflammatory activity, was a result of a preventive treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Male
  • Pancreatic Elastase
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology
  • Pulmonary Emphysema / chemically induced*
  • Pulmonary Emphysema / pathology
  • Pulmonary Emphysema / prevention & control
  • Rats
  • Rats, Inbred Lew
  • Recombinant Proteins / therapeutic use
  • Respiratory Function Tests
  • Stem Cell Factor / therapeutic use*

Substances

  • Recombinant Proteins
  • Stem Cell Factor
  • Granulocyte Colony-Stimulating Factor
  • Pancreatic Elastase