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Published ahead of print on July 25, 2003, doi:10.1164/rccm.200304-467OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 6, September 2003, 692-699

A more recent version of this article appeared on September 15, 2003
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Submitted on April 17, 2003
Accepted on July 9, 2003

Surfactant Protein-A and phosphatidylglycerol suppress type-IIA phospholipase A2 synthesis via NF-{kappa}B

Yong-Zheng WU1, Samir MEDJANE1, Sophie CHABOT1, Flavia Saldanha KUBRUSLY2, Isaias RAW, Michel CHIGNARD1, and Lhousseine TOUQUI*

1 Molecular medicine, Institut Pasteur, Paris, France, 2 Instituto Butantan, Sao Paulo, Brazil

* To whom correspondence should be addressed. E-mail: touqui{at}pasteur.fr.

We previously showed that surfactant inhibits the synthesis of type-IIA secretory phospholipase A2 by alveolar macrophages. These cells have been identified as the main source of this enzyme in an animal model of acute lung injury. The aim of the present study was to identify the surfactant components involved in the inhibition of type-IIA secretory phospholipase A2 expression in alveolar macrophages and the signaling pathways which mediate this inhibition. Our results show that various surfactant preparations can inhibit type-IIA secretory phospholipase A2 expression in endotoxin-stimulated alveolar macrophages. Both the surfactant protein-A and the surfactant phospholipid fraction inhibit this expression. The surfactant phospholipid dioleylphosphatidylglycerol abolishes type-IIA secretory phospholipase A2 expression whereas dipalmitoylphosphatidylcholine does not. Chromatographic analysis and confocal microscopy revealed that phosphatidylglycerol was rapidly incorporated and metabolized by alveolar macrophages, and that its metabolites accumulate in the cytosol. NF-{kappa}B modulates type-IIA secretory phospholipase A2 expression in endotoxin-activated alveolar macrophages, and surfactant preparations, surfactant phospholipid fraction, surfactant protein-A and dioleylphosphatidylglycerol indeed suppressed NF-{kappa}B activation. In summary, our results show that surfactant protein-A and dioleylphosphatidylglycerol play a role in the surfactant-mediated inhibition of type-IIA secretory phospholipase A2 expression in alveolar macrophages and that this inhibition occurs via a down-regulation of NF-{kappa}B activation.
Key words: Surfactant, phospholipase A2, NF-kB, alveolar macrophages




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