HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 23, 20461-20474, June 6, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/23/20461    most recent M212697200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Capote, K. R. Articles by Possmayer, F. Search for Related Content PubMed PubMed Citation Articles by Capote, K. R. Articles by Possmayer, F. Social Bookmarking                      What's this?

Pulmonary Surfactant Protein-A (SP-A) Restores the Surface Properties of Surfactant after Oxidation by a Mechanism That Requires the Cys⁶ Interchain Disulfide Bond and the Phospholipid Binding Domain^*

Karina Rodriguez Capote   ¶, Francis X. McCormack || and Fred Possmayer  **

From the Departments of Obstetrics/Gynecology and Biochemistry, Canadian Institutes of Health Research Group in Fetal and Neonatal Health and Development, University of Western Ontario, London N6A 5A5, Canada, the Departamento de Bioquímica, Instituto Superior de Ciencias Médicas de la Habana-Instituto de Ciencias Básicas y Preclínicas Victoria de Girón, Habana, Cuba, and the ^||Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0564

Reactive oxygen species produced by activated leuko-cytes in the alveolar epithelial lining fluid have been implicated in the inactivation of pulmonary surfactant and the impairment of lung function. Oxidation of bovine lipid extract surfactant (BLES), a therapeutic surfactant, with hypochlorous acid (H-BLES) or the Fenton reaction (F-BLES) led to temporary increases in conjugated dienes and formation of malondialdehyde and 4-hydroxy-2-nonenal. Electrospray ionization mass spectrometry revealed the appearance of lipid hydroperoxides, peroxides, lysophospholipids, and free fatty acids. Captive bubble tensiometer studies of H-BLES demonstrated prolonged adsorption times, film instability at low surface tensions during film compression, and reduced respreadability during film expansion. F-BLES exhibited prolonged adsorption times, a marked effect on increasing compressibility during compression, and a lesser effect on reducing respreadability on expansion. Addition of native bovine or rat surfactant-associated protein A (SP-A) reversed the effects of oxidation on surfactant biophysical properties. Studies using mutant recombinant rat SP-As indicated that an intact carbohydrate recognition domain and disulfide-dependent oligomeric assembly are critical for these effects, but the collagen-like region is not required. We conclude that SP-A can reverse the detrimental effects of surfactant oxidation on the biophysical properties of surfactant, by a mechanism that is dependent on interchain disulfide bond formation and the C-terminal domains of the protein.

Received for publication, December 12, 2002 , and in revised form, February 21, 2003.

^* This work was supported in part by a Group Grant from the Canadian Institutes of Health Research and by National Institutes of Health Grant HL68861. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Supported by a Canadian Institutes of Health Research-Canadian Lung Association Fellowship.

^** To whom correspondence should be addressed: London Health Sciences Centre, 339 Windermere Rd., London, Ontario N6A 5A5, Canada. Tel.: 519-685-8500 (ext. 34938); Fax: 519-663-3388; E-mail: fpossmay{at}uwo.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Orgeig, W. Bernhard, S. C. Biswas, C. B. Daniels, S. B. Hall, S. K. Hetz, C. J. Lang, J. N. Maina, A. K. Panda, J. Perez-Gil, et al. The anatomy, physics, and physiology of gas exchange surfaces: is there a universal function for pulmonary surfactant in animal respiratory structures? Integr. Comp. Biol., October 1, 2007; 47(4): 610 - 627. [Abstract] [Full Text] [PDF]

				T. C. Bailey, A. A. Maruscak, A. Petersen, S. White, J. F. Lewis, and R. A. W. Veldhuizen Physiological effects of oxidized exogenous surfactant in vivo: effects of high tidal volume and surfactant protein A Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L703 - L709. [Abstract] [Full Text] [PDF]

				B. Janic, T. M. Umstead, D. S. Phelps, and J. Floros Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L317 - L325. [Abstract] [Full Text] [PDF]

				T. C. Bailey, K. A. Da Silva, J. F. Lewis, K. Rodriguez-Capote, F. Possmayer, and R. A. W. Veldhuizen Physiological and inflammatory response to instillation of an oxidized surfactant in a rat model of surfactant deficiency J Appl Physiol, May 1, 2004; 96(5): 1674 - 1680. [Abstract] [Full Text] [PDF]

				W. Huang, G. Wang, D. S. Phelps, H. Al-Mondhiry, and J. Floros Human SP-A genetic variants and bleomycin-induced cytokine production by THP-1 cells: effect of ozone-induced SP-A oxidation Am J Physiol Lung Cell Mol Physiol, March 1, 2004; 286(3): L546 - L553. [Abstract] [Full Text] [PDF]