title: Lack of group X secreted phospholipase A₂ increases survival following pandemic H1N1 influenza infection.
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.
authors.affiliation: Immune Diagnostics & Research, Toronto, Ontario, Canada.
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Kelvin
authors.affiliation: Division of Vascular Surgery, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network and the University of Toronto, Toronto, Ontario, Canada.
authors.forename: Norbert
authors.initials: N
authors.lastname: Degousee
authors.affiliation: Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Banner
authors.affiliation: Division of Vascular Surgery, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network and the University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eva
authors.initials: E
authors.lastname: Stefanski
authors.affiliation: 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.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Leόn
authors.affiliation: Division of Cardiology, Trousseau Hospital, Tours University Hospital Center and EA 4245, Francois Rabelais University, Tours, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Angoulvant
authors.affiliation: 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.
authors.forename: Stéphane G
authors.initials: SG
authors.lastname: Paquette
authors.affiliation: 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.
authors.forename: Stephen S H
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Blood Systems Research Institute, San Francisco, CA 2-Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Danesh
authors.affiliation: Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Robbins
authors.affiliation: Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Hossein
authors.initials: H
authors.lastname: Noyan
authors.affiliation: 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.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Husain
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 CNRS and Université de Nice Sophia Antipolis, IPMC, Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Lambeau
authors.affiliation: Departments of Chemistry and Biochemistry, University of Washington, Seattle, Washington, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gelb
authors.affiliation: 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.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kelvin
authors.affiliation: Division of Vascular Surgery, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network and the University of Toronto, Toronto, Ontario, Canada.
authors.forename: Barry B
authors.initials: BB
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D054509:Group X Phospholipases A2 / Q000172:deficiency* / Q000235:genetics; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000821:virology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D054509:Group X Phospholipases A2
keywords: H1N1 pandemic influenza; Host response; Inflammation; Influenza; Leukotrienes; Lipoxin A(4); Pathogenesis; Phospholipids; Prostaglandins; Secreted phospholipase A(2)
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