Kelvin, Alyson A. and Degousee, Norbert and Banner, David and Stefanski, Eva and Leόn, Albert J. and Angoulvant, Denis and Paquette, Stéphane G. and Huang, Stephen S.H. and Danesh, Ali and Robbins, Clinton S. and Noyan, Hossein and Husain, Mansoor and Lambeau, Gérard and Gelb, Michael and Kelvin, David J. and Rubin, Barry B. (2014) Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection. Virology, Vol. 454-455 , p. 78-92. ISSN 0042-6822. eISSN 1096-0341. Article.
The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 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-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 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 sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.
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