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Bronchoalveolar lavage fluid from preterm infants with chorioamnionitis inhibits alveolar epithelial repair
Jasper V Been1, Luc J I Zimmermann, Anne Debeer
1Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, the Netherlands. jasper.been@mumc.nl
Insights
Antenatal steroids enhance bronchoalveolar lavage fluid's ability to repair lung epithelial cells in preterm infants. Conversely, chorioamnionitis impairs this healing capacity, potentially contributing to adverse lung development.
Area of Science:
- Neonatal Medicine
- Pulmonary Biology
- Cellular Biology
Background:
- Preterm infants are vulnerable to lung injury.
- Chorioamnionitis and antenatal steroids impact lung maturation, but chorioamnionitis is linked to adverse lung development.
- Investigating bronchoalveolar lavage fluid (BALF) from preterm infants to assess its role in alveolar epithelial repair after injury.
Purpose of the Study:
- To evaluate the effect of BALF from preterm infants on in vitro alveolar epithelial repair.
- To determine if exposure to chorioamnionitis or antenatal steroids influences BALF's repair capacity.
- To examine the roles of keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF) in BALF-mediated repair.
Main Methods:
- A translational model using wounded A549 cell monolayers was developed.
- BALF was applied to wounded cells, and wound closure was quantified.
- BALF composition (KGF, VEGF) was analyzed, and growth factor effects on repair were tested.
Main Results:
- BALF from infants exposed to antenatal steroids significantly enhanced epithelial repair.
- Chorioamnionitis exposure was associated with reduced BALF wound-healing capacity.
- BALF from chorioamnionitis-exposed infants had lower KGF and VEGF levels, which correlated with repair capacity.
Conclusions:
- Antenatal steroids improve BALF's alveolar epithelial repair potential in preterm infants.
- Chorioamnionitis is linked to decreased BALF-mediated wound healing capacity.
- The study could not establish a definitive role for KGF and VEGF in these processes, but impaired repair may contribute to adverse lung outcomes.
Background:
Preterm infants are highly susceptible to lung injury. While both chorioamnionitis and antenatal steroids induce lung maturation, chorioamnionitis is also associated with adverse lung development. We investigated the ability of bronchoalveolar lavage fluid (BALF) from ventilated preterm infants to restore alveolar epithelial integrity after injury in vitro, depending on whether or not they were exposed to chorioamnionitis or antenatal steroids. For this purpose, a translational model for alveolar epithelial repair was developed and characterised.
Methods:
BALF was added to mechanically wounded monolayers of A549 cells. Wound closure was quantified over time and compared between preterm infants (gestational age < 32 wks) exposed or not exposed to chorioamnionitis and antenatal steroids (>or= 1 dose). Furthermore, keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF) were quantified in BALF, and their ability to induce alveolar epithelial repair was evaluated in the model.
Results:
On day 0/1, BALF from infants exposed to antenatal steroids significantly increased epithelial repair (40.3 +/- 35.5 vs. -6.3 +/- 75.0% above control/mg protein), while chorioamnionitis decreased wound-healing capacity of BALF (-2.9 +/- 87.1 vs. 40.2 +/- 36.9% above control/mg protein). BALF from patients with chorioamnionitis contained less KGF (11 (0-27) vs. 0 (0-4) pg/ml) and less detectable VEGF (66 vs. 95%) on day 0. BALF levels of VEGF and KGF correlated with its ability to induce wound repair. Moreover, KGF stimulated epithelial repair dose-dependently, although the low levels in BALF suggest KGF is not a major modulator of BALF-induced wound repair. VEGF also stimulated alveolar epithelial repair, an effect that was blocked by addition of soluble VEGF receptor-1 (sVEGFr1/Flt-1). However, BALF-induced wound repair was not significantly affected by addition of sVEGFr1.
Conclusion:
Antenatal steroids improve the ability of BALF derived from preterm infants to stimulate alveolar epithelial repair in vitro. Conversely, chorioamnionitis is associated with decreased wound-healing capacity of BALF. A definite role for KGF and VEGF in either process could not be established. Decreased ability to induce alveolar epithelial repair after injury may contribute to the association between chorioamnionitis and adverse lung development in mechanically ventilated preterm infants.
