Suppression of cell proliferation and programmed cell death by dexamethasone during postnatal lung development

Abstract

Prematurely born babies are often treated with glucocorticoids. We studied the consequences of an early postnatal and short dexamethasone treatment (0.1–0.01 μg/g, days 1–4) on lung development in rats, focusing on its influence on peaks of cell proliferation around day 4 and of programmed cell death at days 19–21. By morphological criteria, we observed a dexamethasone-induced premature maturation of the septa ( day 4), followed by a transient septal immatureness and delayed alveolarization leading to complete rescue of the structural changes. The numbers of proliferating (anti-Ki67) and dying cells (TdT-mediated dUTP nick end labeling) were determined and compared with controls. In dexamethasone-treated animals, both the peak of cell proliferation and the peak of programmed cell death were reduced to baseline, whereas the expression of tissue transglutaminase (transglutaminase-C), another marker for postnatal lung maturation, was not significantly altered. We hypothesize that a short neonatal course of dexamethasone leads to severe but transient structural changes of the lung parenchyma and influences the balance between cell proliferation and cell death even in later stages of lung maturation.

Developmental alveolarization of the mouse lung

“…Lungs were obtained from 129/SV mice according to Schittny and coworkers (1997;Luyet et al, 2002) between postnatal days 2 and 125. Briefly, after the lung collapsed in the closed thorax due to a punctuation of the diaphragm, the airspace was filled by tracheal installation with freshly prepared solution of 4% paraformaldehyde in phosphate buffered saline (10 mM sodium phosphate, containing 127 mM sodium chloride, pH 7.4) at a constant pressure of 20 cm water column.…”

Lung Diseases - Selected State of the Art Reviews

“…During organ development, cells must pass through the various cell cycle stages in order to allow for continued remodelling. This process is essential to proper lung development (Bruce et al, 1999;Luyet et al, 2000). Consequently, the redox potential must also cycle continuously ( Figure 3).…”

“…A more oxidized state will also induce cell death by apoptosis. (Adapted from Schafer FQ et al, 2001) The link between redox potential and BPD can be explained by an exacerbated apoptosis rate caused by an abnormally elevated redox potential (Luyet et al, 2000). Lung samples from premature baboons with BPD (Das et al, 2004) showed a large number of apoptotic events.…”

“…On histology, 30% of alveolar cells were in an apoptotic state . During normal alveolar development, however, about 10% of cells die by apoptosis (Luyet et al, 2000), in order to thin the septa between alveoli for more efficient gas exchange (Bruce et al, 1999;Luyet et al, 2000). Various factors may contribute to a shift in redox potential to a more oxidized state ( Figure 3, dashed line).…”

High resolution tomographic imaging of the alveolar region of the mammalian lung

“…Rat lung samples, prepared according to Tschanz and Burri [123] and Luyet et al [124] were used as test objects. Briefly, lungs of SpragueDawley rats were filled with 2.5 % glutaraldehyde (CH 2 (CH 2 CHO) 2 ) in 0.03 m potassium-phosphate buffer (pH 7.4) by instillation via tracheotomy at a constant pressure of 20 cm water column.…”