Elastase-induced lung emphysema in rats is not reduced by hematopoietic growth factors when applied preventionally.
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.
Schmiedl
Andreas
A
Department of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Schmiedl.Andreas@mh-hannover.de
Lempa
Tobias
T
Hoymann
Heinz G
HG
Rittinghausen
Susanne
S
Popa
Daniela
D
Tschernig
Thomas
T
Fehrenbach
Heinz
H
Pabst
Reinhard
R
Hoeper
Marius M
MM
Hohlfeld
Jens M
JM
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*
D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D010196:Pancreatic Elastase