| Lysophospholipid and fatty acid inhibition of pulmonary surfactant: non-enzymatic models of phospholipase A2 surfactant hydrolysis. | |
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MedLine Citation:
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PMID: 16376294 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Secretory A(2) phospholipases (sPLA(2)) hydrolyze surfactant phospholipids cause surfactant dysfunction and are elevated in lung inflammation. Phospholipase-mediated surfactant hydrolysis may disrupt surfactant function by generation of lysophospholipids and free fatty acids and/or depletion of native phospholipids. In this study, we quantitatively assessed multiple mechanisms of sPLA(2)-mediated surfactant dysfunction using non-enzymatic models including supplementation of surfactants with exogenous lysophospholipids and free fatty acids. Our data demonstrated lysophospholipids at levels >or=10 mol% of total phospholipid (i.e., >or=10% hydrolysis) led to a significant increase in minimum surface tension and increased the time to achieve a normal minimum surface tension. Lysophospholipid inhibition of surfactant function was independent of the lysophospholipid head group or total phospholipid concentration. Free fatty acids (palmitic acid, oleic acid) alone had little effect on minimum surface tension, but did increase the maximum surface tension and the time to achieve normal minimum surface tension. The combined effect of equimolar free fatty acids and lysophospholipids was not different from the effect of lysophospholipids alone for any measurement of surfactant function. Surfactant proteins did not change the percent lysophospholipids required to increase minimum surface tension. As a mechanism that causes surfactant dysfunction, depletion of native phospholipids required much greater change (equivalent to >80% hydrolysis) than generation of lysophospholipids. In summary, generation of lysophospholipids is the principal mechanism of phospholipase-mediated surfactant injury in our non-enzymatic models. These models and findings will assist in understanding more complex in vitro and in vivo studies of phospholipase-mediated surfactant injury. |
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Authors:
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R Duncan Hite; Michael C Seeds; Randy B Jacinto; Bonnie L Grier; B Moseley Waite; David A Bass |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2005-11-21 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1720 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2005 Dec |
Date Detail:
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Created Date: 2006-02-13 Completed Date: 2006-03-23 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 14-21 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Section on Pulmonary and Critical Care, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. dhite@wfubmc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Fatty Acids / pharmacology* Lysophospholipids / pharmacology* Models, Chemical Phospholipases A / metabolism* Phospholipases A2 Pulmonary Surfactants / antagonists & inhibitors*, chemistry, metabolism Surface Tension / drug effects Swine |
| Grant Support | |
ID/Acronym/Agency:
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HL64226/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids; 0/Lysophospholipids; 0/Pulmonary Surfactants; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2 |
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