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Virology. 2014 Apr;454-455:78-92. doi: 10.1016/j.virol.2014.01.030. Epub 2014 Feb 25.

Lack of group X secreted phospholipase A₂ increases survival following pandemic H1N1 influenza infection.

Author information

1
Immune Diagnostics & Research, Toronto, Ontario, Canada.
2
Division of Vascular Surgery, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network and the University of Toronto, Toronto, Ontario, Canada.
3
Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
4
Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong, China.
5
Division of Cardiology, Trousseau Hospital, Tours University Hospital Center and EA 4245, Francois Rabelais University, Tours, France.
6
Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
7
Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
8
Blood Systems Research Institute, San Francisco, CA 2-Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
9
Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Heart & Stroke Richard Lewar Centre of Excellence, University of Toronto, University Health Network, Toronto, Ontario, Canada.
10
Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS and Université de Nice Sophia Antipolis, IPMC, Sophia Antipolis, 06560 Valbonne, France.
11
Departments of Chemistry and Biochemistry, University of Washington, Seattle, Washington, USA.
12
Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong, China; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Sezione di Microbiologia Sperimentale e Clinica, Dipartimento di Scienze Biomediche, Universita׳ degli Studi di Sassari, Sassari, Italy. Electronic address: dkelvin@uhnresearch.ca.

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:

H1N1 pandemic influenza; Host response; Inflammation; Influenza; Leukotrienes; Lipoxin A(4); Pathogenesis; Phospholipids; Prostaglandins; Secreted phospholipase A(2)

PMID:
24725934
PMCID:
PMC4106042
DOI:
10.1016/j.virol.2014.01.030
[Indexed for MEDLINE]
Free PMC Article

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