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Published on: August 7, 2017
Mitogenic activity of tracheal effluents from premature infants with chronic lung disease
Mika Saito1, Hiroyuki Ichiba, Toshiaki Yokoi
1Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
Insights
Growth factors in tracheal effluents from infants with chronic lung disease (CLD) promote cell proliferation and collagen production. Transforming growth factor beta-1 (TGF-beta(1)) may worsen CLD, while hepatocyte growth factor (HGF) might aid lung repair.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Neonatology
Background:
- Lung injury in newborns can lead to chronic lung disease (CLD).
- Altered growth factor expression and release are implicated in CLD pathogenesis.
- These factors may disrupt normal postnatal lung development.
Purpose of the Study:
- To investigate the in vitro effects of tracheal effluents from CLD infants on lung cells.
- To characterize the impact of these effluents on cell proliferation and collagen production.
- To identify specific growth factors involved in these processes.
Main Methods:
- Human fetal lung fibroblast and alveolar epithelial cell lines were exposed to tracheal effluents.
- Cell proliferation was measured via [3H]-thymidine uptake.
- Collagen production was assessed using [3H]-proline incorporation.
- Growth factor activity was determined using antibodies and exogenous growth factors.
Main Results:
- Tracheal effluents significantly increased proliferation in both cell types (up to 10.2-fold in fibroblasts, 3.1-fold in epithelial cells).
- Collagen production in fibroblasts increased dose-dependently, peaking at 177% of baseline.
- Antibodies against TGF-beta(1) and HGF partially inhibited the effects of the effluents.
- Exogenous TGF-beta(1) and HGF mimicked the effects observed with tracheal effluents.
Conclusions:
- Newborns with CLD release potent mitogenic and differentiating substances in tracheal effluents.
- TGF-beta(1) in effluents may contribute to CLD fibrosis.
- HGF in effluents might promote epithelialization, potentially aiding lung repair.
Abstract:
Lung injury alters the expression and release of growth factors that disrupt postnatal pulmonary development in newborns and causes chronic lung disease (CLD). The effect of these factors, released into the airways of newborns with CLD, on cell proliferation and collagen production was characterized in vitro. Human fetal lung fibroblast and alveolar-epithelial-like cell lines (FHs 738Lu and A549, respectively) were exposed to tracheal effluents from infants with CLD (mean gestation, 24.7 +/- 0.9 wk; birth weight, 666 +/- 85 g; postnatal age, 0-62 d). In both cell types, proliferation was assessed by measuring [(3)H]-thymidine uptake; in fibroblasts, collagen production was analyzed by measuring [(3)H]-proline incorporation. The activity of specific growth factors in effluents was determined using anti-growth factor antibodies and the growth factors themselves. Growth factors in tracheal effluents promoted proliferation in a dose-dependent manner and caused up to a 10.2- and 3.1-fold increase in thymidine uptake by fibroblasts and epithelial cells, respectively. Collagen production by fibroblasts increased dose dependently, peaking at 177% of baseline. Antibody against transforming growth factor beta-1 (TGF-beta(1)) inhibited proliferation and the increase in collagen production by 31% (p = 0.01) and 14% (p = 0.045), respectively. Antibody against hepatocyte growth factor (HGF) inhibited proliferation of epithelial cells (25%, p = 0.039). The effects of exogenous TGF-beta(1) on fibroblasts and HGF on epithelial cells resembled those of tracheal effluents. Potent mitogenic and differentiating substances are released into the tracheal effluents of newborns with CLD. TGF-beta(1) may worsen CLD by inducing fibrosis whereas HGF may favor resolution by promoting epithelialization.
