Surfactant phospholipid changes after antigen challenge: a role for phosphatidylglycerol in dysfunction
- 1 April 2005
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Lung Cellular and Molecular Physiology
- Vol. 288 (4), L610-L617
- https://doi.org/10.1152/ajplung.00273.2004
Abstract
In asthma, inflammation-mediated surfactant dysfunction contributes to increased airway resistance, but the mechanisms for dysfunction are not understood. To test mechanisms that alter surfactant function, atopic asthmatics underwent endobronchial antigen challenge and bronchoalveolar lavage (BAL). BAL fluids were sequentially separated into cells, surfactant, and supernatant, and multiple end points were analyzed. Each end point's unique relationship to surfactant dysfunction was determined. Our results demonstrate that minimum surface tension (γmin) of surfactant after antigen challenge was significantly increased with a spectrum of responses that included dysfunction in 6 of 13 asthmatics. Antigen challenge significantly altered the partitioning of surfactant phospholipid measured as a decreased ratio of large surfactant aggregates (LA) to small surfactant aggregates (SA), LA/SA ratio. Phosphatidylglycerol (PG) was significantly reduced in the LA of the dysfunctional asthmatic BALs. There was a corresponding significant increase in the ratio of phosphatidylcholine to PG, which strongly correlated with both increased γminand decreased LA/SA. Altered surfactant phospholipid properties correlated with surfactant dysfunction as well or better than either increased eosinophils or protein. Secretory phospholipase activity, measured in vitro, increased after antigen challenge and may explain the decrease in surfactant PG. In summary, alteration of phospholipids, particularly depletion of PG, in the LA of surfactant may be an important mechanism in asthma-associated surfactant dysfunction.Keywords
This publication has 29 references indexed in Scilit:
- Lysophospholipid generation and phosphatidylglycerol depletion in phospholipase A2-mediated surfactant dysfunctionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- A Novel Phosphatidylglycerol-Selective Phospholipase A2 from MacrophagesBiochemistry, 1999
- Protein–Lipid Interactions and Enzyme Requirements for Light Subtype Generation on Cycling Reconstituted SurfactantBiochemical and Biophysical Research Communications, 1998
- Antigen-induced generation of lyso-phospholipids in human airways.The Journal of Experimental Medicine, 1996
- Surfactant dysfunction develops when the immunized guinea‐pig is challenged with ovalbumin aerosolClinical and Experimental Allergy, 1995
- Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome.JCI Insight, 1991
- Biophysical inhibition of synthetic phospholipid-lung surfactant apoprotein admixtures by plasma proteinsChemistry and Physics of Lipids, 1991
- [35] Assay and purification of phospholipase A2 from human synovial fluid in rheumatoid arthritisMethods in Enzymology, 1991
- The stability of peripheral airwaysRespiration Physiology, 1970
- A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATIONCanadian Journal of Biochemistry and Physiology, 1959