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Virology
Volumes 454?455, April 2014, Pages 78?92
Cover image
Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection
Alyson A. Kelvina, 1,
Norbert Degouseeb, 1,
David Bannerc,
Eva Stefanskib,
Alberto J. Leόnc, d,
Denis Angoulvante,
St?phane G. Paquettec, f,
Stephen S.H. Huangc, g,
Ali Daneshh,
Clinton S. Robbinsc,
Hossein Noyanc,
Mansoor Husainc, i,
Gerard Lambeauj,
Michael Gelbk,
David J. Kelvinc, d, f, g, l, Corresponding author contact information, E-mail the corresponding author,
Barry B. Rubinb
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Open Access
Highlights
?
We investigated GX-sPLA2−/− mice infected with pandemic H1N1.
?
GX−/− mice had increased survival and significantly lower eicosanoids in BAL fluid.
?
Lung RNA analysis identified earlier and increased induction of T and B cell responses in GX−/− mice.
?
GX may initiate influenza inflammation; inhibition promotes adaptive immunity and survival.
?
Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.
Abstract
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.
Keywords
Secreted phospholipase A2;
Influenza;
Host response;
Phospholipids;
H1N1 pandemic influenza;
Leukotrienes;
Prostaglandins;
Lipoxin A4;
Pathogenesis;
Inflammation
full article
Volumes 454?455, April 2014, Pages 78?92
Cover image
Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection
Alyson A. Kelvina, 1,
Norbert Degouseeb, 1,
David Bannerc,
Eva Stefanskib,
Alberto J. Leόnc, d,
Denis Angoulvante,
St?phane G. Paquettec, f,
Stephen S.H. Huangc, g,
Ali Daneshh,
Clinton S. Robbinsc,
Hossein Noyanc,
Mansoor Husainc, i,
Gerard Lambeauj,
Michael Gelbk,
David J. Kelvinc, d, f, g, l, Corresponding author contact information, E-mail the corresponding author,
Barry B. Rubinb
Show more
Get rights and content
Open Access
Highlights
?
We investigated GX-sPLA2−/− mice infected with pandemic H1N1.
?
GX−/− mice had increased survival and significantly lower eicosanoids in BAL fluid.
?
Lung RNA analysis identified earlier and increased induction of T and B cell responses in GX−/− mice.
?
GX may initiate influenza inflammation; inhibition promotes adaptive immunity and survival.
?
Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.
Abstract
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.
Keywords
Secreted phospholipase A2;
Influenza;
Host response;
Phospholipids;
H1N1 pandemic influenza;
Leukotrienes;
Prostaglandins;
Lipoxin A4;
Pathogenesis;
Inflammation
full article