Secretory group V phospholipase A2 regulates acute lung injury and neutrophilic inflammation caused by LPS in mice.
We investigated the regulatory role of 14-kDa secretory group V phospholipase A(2) (gVPLA(2)) in the development of acute lung injury (ALI) and neutrophilic inflammation (NI) caused by intratracheal administration of LPS. Experiments were conducted in gVPLA(2) knockout (pla2g5(-/-)) mice, which lack the gene, and gVPLA(2) wild-type littermate control (pla2g5(+/+)) mice. Indices of pulmonary injury were evaluated 24 h after intratracheal administration of LPS. Expression of gVPLA(2) 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 gVPLA(2) 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 gVPLA(2), before LPS administration. Our data demonstrate that gVPLA(2) is an inducible protein in pla2g5(+/+) mice but not in pla2g5(-/-) mice within 24 h after LPS treatment. Specific inhibition of gVPLA(2) with MCL-3G1 or gene-targeted mice lacking gVPLA(2) blocks ALI and attenuates NI caused by LPS.
Muñoz
Nilda M
NM
Dept. of Medicine, M6076, Univ. of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA.
Meliton
Angelo Y
AY
Meliton
Lucille N
LN
Dudek
Steven M
SM
Leff
Alan R
AR
D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015633:Extravascular Lung Water / Q000378:metabolism; D054505:Group V Phospholipases A2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008170:Lung Compliance / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015290:Second Messenger Systems / Q000276:immunology
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009195:Peroxidase; D054505:Group V Phospholipases A2