Submitted on November 24, 2008
Revised on March 2, 2009
Accepted on March 8, 2009
Secretory Group V Phospholipase A2 Regulates Acute Lung Injury and Neutrophilic Inflammation Caused by LPS in Mice
Nilda M Munoz1, Angelo Yuk Meliton1, Lucille N Meliton1, Steven M. Dudek1, and Alan R. Leff1*
1 The University of Chicago
* To whom correspondence should be addressed. E-mail: aleff{at}medicine.bsd.uchicago.edu.
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 intra-tracheal administration of LPS. Experiments were conducted in gVPLA2 knock-out (pla2g5-/-) mice, which lack the gene, and gVPLA2 wild-type littermate control (pla2g5+/+) mice. Indices of pulmonary injury were evaluated 24 h after intra-tracheal administration of LPS. Expression of gVPLA2 in microsections of airways and mRNA content in lung homogenates were increased substantially in pla2g5+/+ mice after LPS infusion compared to saline-treated pla2g5+/+ mice. LPS also caused a) reduced transthoracic static compliance, b) lung edema, c) neutrophilic infiltration, and d) 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, prior to LPS administration. Our data demonstrate that gVPLA2 is an inducible protein in pla2g5+/+ mice but not in pla2g5-/- mice within 24 h after LPS infusion. Specific inhibition of gVPLA2 with MCL-3G1 or gene targeted mice lacking gVPLA2 blocks ALI and attenuates NI caused by LPS.
