title: Elastase-induced lung emphysema in rats is not reduced by hematopoietic growth factors when applied preventionally.
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.
authors.affiliation: Department of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Schmiedl.Andreas@mh-hannover.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmiedl
authors.forename: Tobias
authors.initials: T
authors.lastname: Lempa
authors.forename: Heinz G
authors.initials: HG
authors.lastname: Hoymann
authors.forename: Susanne
authors.initials: S
authors.lastname: Rittinghausen
authors.forename: Daniela
authors.initials: D
authors.lastname: Popa
authors.forename: Thomas
authors.initials: T
authors.lastname: Tschernig
authors.forename: Heinz
authors.initials: H
authors.lastname: Fehrenbach
authors.forename: Reinhard
authors.initials: R
authors.lastname: Pabst
authors.forename: Marius M
authors.initials: MM
authors.lastname: Hoeper
authors.forename: Jens M
authors.initials: JM
authors.lastname: Hohlfeld
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D008297:Male; D010196:Pancreatic Elastase; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use; D012129:Respiratory Function Tests; D019089:Stem Cell Factor / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D010196:Pancreatic Elastase