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

: Schmiedl, A.; Lempa, T.; Hoymann, H.G.; Rittinghausen, S.; Popa, D.; Tschernig, T.; Fehrenbach, H.; Pabst, R.; Hoeper, M.M.; Hohlfeld, J.M.


Virchows Archiv 452 (2008), Nr.6, S.675-688
ISSN: 0945-6317
ISSN: 1432-2307
Fraunhofer ITEM ()
lung emphysema; stem cell factor; lung function; rat; stereology

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 mu g/ h 5-bromo2- 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.