Transient Exposure of Pulmonary Surfactant to Hyaluronan Promotes Structural and Compositional Transformations into a Highly Active State

Autor: H. W. Taeusch, Ralf P. Richter, A. Cruz, Elena Lopez-Rodriguez, Jesús Pérez-Gil
Přispěvatelé: Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires (DCM - I2BM), Département de Chimie Moléculaire (DCM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Dept. Bioquimica, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Models
Molecular
Surface Properties
Swine
Phospholipid
010402 general chemistry
01 natural sciences
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Pulmonary surfactant
Membrane Biology
medicine
Meconium aspiration syndrome
Animals
[CHIM]Chemical Sciences
Hyaluronic Acid
Respiratory system
Molecular Biology
Phospholipids
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Pulmonary Surfactant-Associated Protein B
Lung
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactants
Cell Biology
Polymer
medicine.disease
Pulmonary Surfactant-Associated Protein C
3. Good health
0104 chemical sciences
medicine.anatomical_structure
Membrane
Models
Chemical
chemistry
Biophysics
Thermodynamics
Adsorption
Bronchoalveolar Lavage Fluid
Membrane biophysics
Protein Binding
Zdroj: Journal of Biological Chemistry
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2013, 288 (41), pp.29872-29881. ⟨10.1074/jbc.M113.493957⟩
ISSN: 0021-9258
1083-351X
Popis: Pulmonary surfactant is a lipid-protein complex that lowers surface tension at the respiratory air-liquid interface, stabilizing the lungs against physical forces tending to collapse alveoli. Dysfunction of surfactant is associated with respiratory pathologies such as acute respiratory distress syndrome or meconium aspiration syndrome where naturally occurring surfactant-inhibitory agents such as serum, meconium, or cholesterol reach the lung. We analyzed the effect of hyaluronan (HA) on the structure and surface behavior of pulmonary surfactant to understand the mechanism for HA-promoted surfactant protection in the presence of inhibitory agents. In particular, we found that HA affects structural properties such as the aggregation state of surfactant membranes and the size, distribution, and order/packing of phase-segregated lipid domains. These effects do not require a direct interaction between surfactant complexes and HA and are accompanied by a compositional reorganization of large surfactant complexes that become enriched with saturated phospholipid species. HA-exposed surfactant reaches very high efficiency in terms of rapid and spontaneous adsorption of surfactant phospholipids at the air-liquid interface and shows significantly improved resistance to inactivation by serum or cholesterol. We propose that physical effects pertaining to the formation of a meshwork of interpenetrating HA polymer chains are responsible for the changes in surfactant structure and composition that enhance surfactant function and, thus, resistance to inactivation. The higher resistance of HA-exposed surfactant to inactivation persists even after removal of the polymer, suggesting that transient exposure of surfactant to polymers like HA could be a promising strategy for the production of more efficient therapeutic surfactant preparations. Background: Pulmonary surfactant is inactivated under pathological conditions, making clinical surfactants fail in respiratory therapies. Results: Exposure to a hyaluronan meshwork modifies the structure and composition of surfactant. Conclusion: Transient exposure of surfactant to hyaluronan leads to a higher resistance to inactivation. Significance: Understanding the effects of polymers as additives in surfactant will allow the development of new therapeutic options.
Databáze: OpenAIRE
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