Surfactant phospholipid changes after antigen challenge: a role for phosphatidylglycerol in dysfunction.
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 (gamma(min)) 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 gamma(min) and 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.
Hite
R Duncan
RD
Section of Pulmonary Medicine, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1054, USA. dhite@wfubmc.edu
Seeds
Michael C
MC
Bowton
David L
DL
Grier
Bonnie L
BL
Safta
Anca M
AM
Balkrishnan
Rajesh
R
Waite
B Moseley
BM
Bass
David A
DA
D000485:Allergens / Q000276:immunology*; D017951:Antigen Presentation; D001249:Asthma / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D010713:Phosphatidylcholines / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism; D013500:Surface Tension
D000485:Allergens; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; D010741:Phospholipases A