Lack of group X secreted phospholipase A(2) increases survival following pandemic H1N1 influenza infection

The role of Group X secreted phospholipase A(2) (GX-sPLA(2)) during influenza infection has not been previously investigated. We examined the role of GX-sPLA(2) during H1N1 pandemic influenza infection in a GX-sPLA(2) gene targeted mouse (GX(−/−)) model and found that survival after infection was significantly greater in GX(−/−) mice than in GX(+/+) mice. Downstream products of GX-sPLA(2) activity, PGD(2), PGE(2), LTB(4), cysteinyl leukotrienes and Lipoxin A(4) were significantly lower in GX(−/−) mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX(−/−) mice. Based on the central role of sPLA(2) enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA(2) during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA(2) may be a potential therapeutic target during influenza.