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

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American Physiological Society

RESUMO

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.

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