Meconium impairs pulmonary surfactant by a combined action of cholesterol and bile acids.
Summary of "Meconium impairs pulmonary surfactant by a combined action of cholesterol and bile acids."
Mechanisms for meconium-induced inactivation of pulmonary surfactant as part of the meconium aspiration syndrome in newborn infants, to our knowledge, are not clearly understood. Here we have studied the biophysical mechanisms of how meconium affects surface activity of pulmonary surfactant and whether the membrane-perturbing effects of meconium can be mimicked by exposure of surfactant to a mixture of bile acids and cholesterol. Surface activity of pulmonary surfactant complexes purified from animal lungs was analyzed in the absence and in the presence of meconium in standard surface balances and in a captive bubble surfactometer. We have also evaluated accumulation of surfactant at the air-liquid interface by what we believe to be a novel microtiter plate fluorescent assay, and the effect of meconium components on surfactant membrane fluidity using Laurdan fluorescence thermotropic profiles and differential scanning calorimetry thermograms. Rapid interfacial adsorption, low surface tension upon film compression, efficient film replenishment upon expansion, and thermotropic properties of surfactant complexes are all adversely affected by meconium, and, in a similar manner, they are affected by cholesterol/taurocholate mixtures but not by taurocholate alone. We conclude that inhibition of surfactant by meconium can be mimicked by a bile salt-promoted incorporation of excess cholesterol into surfactant complexes. These results highlight the potential pathogenic role of cholesterol-mobilizing agents as a crucial factor resulting in cholesterol induced alterations of structure and dynamics of surfactant membranes and films.
Affiliation
Departamento Bioquimica, Facultad Biologia, Universidad Complutense, Madrid, Spain.
Journal Details
This article was published in the following journal.
Name: Biophysical journal
ISSN: 1542-0086
Pages: 646-55
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21281579
- DOI: http://dx.doi.org/10.1016/j.bpj.2010.12.3715
Medical and Biotech [MESH] Definitions
Pulmonary Surfactant-associated Protein C
A pulmonary surfactant associated protein that plays a role in alveolar stability by lowering the surface tension at the air-liquid interface. It is a membrane-bound protein that constitutes 1-2% of the pulmonary surfactant mass. Pulmonary surfactant-associated protein C is one of the most hydrophobic peptides yet isolated and contains an alpha-helical domain with a central poly-valine segment that binds to phospholipid bilayers.
Pulmonary Surfactant-associated Protein B
A pulmonary surfactant associated-protein that plays an essential role in alveolar stability by lowering the surface tension at the air-liquid interface. Inherited deficiency of pulmonary surfactant-associated protein B is one cause of RESPIRATORY DISTRESS SYNDROME, NEWBORN.
Meconium Aspiration Syndrome
A condition caused by inhalation of MECONIUM into the LUNG of FETUS or NEWBORN, usually due to vigorous respiratory movements during difficult PARTURITION or respiratory system abnormalities. Meconium aspirate may block small airways leading to difficulties in PULMONARY GAS EXCHANGE and ASPIRATION PNEUMONIA.
Pulmonary Surfactant-associated Protein D
An abundant pulmonary surfactant-associated protein that binds to a variety of lung pathogens and enhances their opsinization and killing by phagocytic cells. Surfactant protein D contains a N-terminal collagen-like domain and a C-terminal lectin domain that are characteristic of members of the collectin family of proteins.
Pulmonary Surfactant-associated Protein A
An abundant pulmonary surfactant-associated protein that binds to a variety of lung pathogens, resulting in their opsinization. It also stimulates MACROPHAGES to undergo PHAGOCYTOSIS of microorganisms. Surfactant protein A contains a N-terminal collagen-like domain and a C-terminal lectin domain that are characteristic of members of the collectin family of proteins.
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