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Am J Physiol Lung Cell Mol Physiol 288: L610-L617, 2005. First published September 3, 2004; doi:10.1152/ajplung.00273.2004
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EDITORIAL FOCUS

Surfactant phospholipid changes after antigen challenge: a role for phosphatidylglycerol in dysfunction

R. Duncan Hite,1 Michael C. Seeds,1,2 David L. Bowton,1,3 Bonnie L. Grier,1 Anca M. Safta,1 Rajesh Balkrishnan,1,4 B. Moseley Waite,1,5 and David A. Bass1,2

1Department of Internal Medicine/Sections of Pulmonary and Critical Care Medicine and 2Molecular Medicine, Departments of 3Anesthesiology, 4Public Health Sciences, and 5Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Submitted 19 July 2004 ; accepted in final form 30 August 2004

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.

phospholipids; phospholipases; surface-active agents; eosinophils; lung injury



Address for reprint requests and other correspondence: R. Duncan Hite, Sect. of Pulmonary and Critical Care Medicine, Wake Forest Univ. School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1054 (E-mail: dhite{at}wfubmc.edu




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