Effect of pulmonary surfactant on TNF-alpha-activated endothelial cells and neutrophil adhesion in vitro.

ABSTRACT

Pulmonary surfactant given to infants and adults with respiratory failure is metabolized and recycled to a large extent. A small proportion also enters the circulation in cases of increased permeability of the alveolar-capillary membrane. We therefore investigated whether exogenous surfactants such as a natural bovine (natSF) or a synthetic (synSF) preparation had an impact on inflammatory conditions involving the adhesion of neutrophils to endothelial cells. Human umbilical cord vein endothelial cells (HUVEC) were plated on coverslips until confluence, activated by tumor necrosis factor-alpha and incubated with or without surfactant in the media. Human neutrophils passed the HUVEC layer in a flow chamber and interactions were visualized using a video microscope. To test if surfactant affected the expression of cell adhesion molecules, RT-PCR analyses were performed for E-selectin, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Using concentrations between 50 and 300 microg/ml of surfactant in the pre-incubation media the number of adherent neutrophils increased by 10-20% at the higher concentration of the natSF (*P < 0.05) whereas the synSF had no effect. Increased neutrophil adhesion was associated with a significant up-regulation of mRNA levels for E-selectin and VCAM-1; mRNA levels for ICAM-1, however, were not affected by the presence of surfactant. These observations indicate that natSF but not synSF might have pro-inflammatory effects when higher amounts of the exogenous dose reach the circulation. This might be explained by different fatty acid profiles, e.g. the presence of arachidonic acid in the natSF or higher concentrations of surfactant-associated protein-C in the synSF.