The effects of dexamethasone and oxygen in ventilated adult sheep with early phase acute respiratory distress syndrome.

Background: Acute respiratory distress syndrome (ARDS) is a life-threating condition with high morbidity and mortality. Inflammation is the main factor in the pathogenesis of ARDS. Therefore systemic corticosteroids are a rational therapeutic approach, but the effect of corticosteroids is still unclear.

Surfactant protein A binds TGF-β1 with high affinity and stimulates the TGF-β pathway.

We were able to demonstrate reversible, specific and high-affinity binding of radioactively-labelled TGF-β1 ((125)I-TGF-β1) to immobilized surfactant protein A (SP-A), with an apparent dissociation constant of 53 picomolar at ∼21. Addition of a 200-fold molar excess of the latency associated peptide (LAP) prevented and dissociated the binding of (125)I-TGF-β1 to SP-A, whereas latent TGF-β1 had no effect. Using a bioassay for TGF-β1 activity--a luciferase reporter assay--we were able to show that SP-A in the presence of TGF-β1 stimulated the TGF-β1 pathway, whereas SP-A alone had no effect.

Comparison of recruitment manoeuvres in ventilated sheep with acute respiratory distress syndrome.

Background: Recruitment manoeuvres are widely used in clinical practice to open the lung and prevent lung injury by derecruitment, although the evidence is still discussed. In this study two different recruitment manoeuvres were compared to no recruitment manoeuvres (control) in ventilated sheep with acute respiratory distress syndrome (ARDS), induced by lung lavage.

Methods: We performed a prospective, randomised study in 26 ventilated sheep with ARDS, to evaluate the effect of two different recruitment manoeuvres on gas exchange, blood pressure and lung injury.

Surfactant protein A influences reepithelialization in an alveolocapillary model system.

Purpose: Restoring the barrier integrity of the alveolar epithelium after injury is pivotal. In the current study, we evaluated the effects of surfactant, surfactant protein A (SP-A), transforming growth factor β (TGF-β), and analogues of SP-A on alveolar epithelial repair. Additionally, we assessed the influence of microvascular endothelial cells on reepithelialization.

Alveolocapillary model system to study alveolar re-epithelialization.

In the present study an in vitro bilayer model system of the pulmonary alveolocapillary barrier was established to investigate the role of the microvascular endothelium on re-epithelialization. The model system, confluent monolayer cultures on opposing sides of a porous membrane, consisted of a human microvascular endothelial cell line (HPMEC-ST1.6R) and an alveolar type II like cell line (A549), stably expressing EGFP and mCherry, respectively.

Dissociation of transforming growth factors β1 and β2 from surfactant protein A (SP-A) by deglycosylation or deoxycholate treatment.

We were able to demonstrate the presence of transforming growth factor β1 and transforming growth factor β2 (TGF-β1,2) in human as well as porcine pulmonary surfactants and SP-A purified from these surfactants. Human SP-A contained 480±74 pg TGF-β1 and 61±16 pg TGF-β2 per mg SP-A and human pulmonary surfactant contained 140±28 pg TGF-β1 and 67±13 TGF-β2 per mg protein. Porcine SP-A contained 306±46 pg TGF-β1 and 43±12 pg TGF-β2 per mg SP-A and porcine pulmonary surfactant contained 75±18 pg TGF-β1 and 22±13 TGF-β2 per mg protein.

IL-1α mediated chorioamnionitis induces depletion of FoxP3+ cells and ileal inflammation in the ovine fetal gut.

Background: Endotoxin induced chorioamnionitis increases IL-1 and provokes an inflammatory response in the fetal ileum that interferes with intestinal maturation. In the present study, we tested in an ovine chorioamnionitis model whether IL-1 is a major cytokine driving the inflammatory response in the fetal ileum.

Method: Sheep bearing singleton fetuses received a single intraamniotic injection of recombinant ovine IL-1α at 7, 3 or 1 d before caesarian delivery at 125 days gestational age (term = 150 days).