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This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/L879    most recent 90580.2008v1 Alert me when this article is cited 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 Google Scholar Articles by Muñoz, N. M. Articles by Leff, A. R. PubMed PubMed Citation Articles by Muñoz, N. M. Articles by Leff, A. R.

Secretory group V phospholipase A₂ regulates acute lung injury and neutrophilic inflammation caused by LPS in mice

¹Section of Pulmonary and Critical Care Medicine, Department of Medicine, and ²Neurobiology Pharmacology and Physiology and Committees on Molecular Medicine, Clinical Pharmacology, and Cell Physiology, University of Chicago, Chicago, Illinois

Submitted 24 November 2008 ; accepted in final form 8 March 2009

We investigated the regulatory role of 14-kDa secretory group V phospholipase A₂ (gVPLA₂) in the development of acute lung injury (ALI) and neutrophilic inflammation (NI) caused by intratracheal administration of LPS. Experiments were conducted in gVPLA₂ knockout (pla2g5^–/–) mice, which lack the gene, and gVPLA₂ wild-type littermate control (pla2g5^+/+) mice. Indices of pulmonary injury were evaluated 24 h after intratracheal administration of LPS. Expression of gVPLA₂ in microsections of airways and mRNA content in lung homogenates were increased substantially in pla2g5^+/+ mice after LPS-administered compared with saline-treated pla2g5^+/+ mice. By contrast, expression of gVPLA₂ was neither localized in LPS- nor saline-treated pla2g5^–/– mice. LPS also caused 1) reduced transthoracic static compliance, 2) lung edema, 3) neutrophilic infiltration, and 4) increased neutrophil myeloperoxidase activity in pla2g5^+/+ mice. These events were attenuated in pla2g5^–/– mice exposed to LPS or in pla2g5^+/+ mice receiving MCL-3G1, a neutralizing MAb directed against gVPLA₂, before LPS administration. Our data demonstrate that gVPLA₂ is an inducible protein in pla2g5^+/+ mice but not in pla2g5^–/– mice within 24 h after LPS treatment. Specific inhibition of gVPLA₂ with MCL-3G1 or gene-targeted mice lacking gVPLA₂ blocks ALI and attenuates NI caused by LPS.

airway inflammation; chemotaxis; pulmonary compliance