title: Group V phospholipase A2 in bone marrow-derived myeloid cells and bronchial epithelial cells promotes bacterial clearance after Escherichia coli pneumonia.
abstract: Group V-secreted phospholipase A(2) (GV sPLA(2)) hydrolyzes bacterial phospholipids and initiates eicosanoid biosynthesis. Here, we elucidate the role of GV sPLA(2) in the pathophysiology of Escherichia coli pneumonia. Inflammatory cells and bronchial epithelial cells both express GV sPLA(2) after pulmonary E. coli infection. GV(-/-) mice accumulate fewer polymorphonuclear leukocytes in alveoli, have higher levels of E. coli in bronchoalveolar lavage fluid and lung, and develop respiratory acidosis, more severe hypothermia, and higher IL-6, IL-10, and TNF-α levels than GV(+/+) mice after pulmonary E. coli infection. Eicosanoid levels in bronchoalveolar lavage are similar in GV(+/+) and GV(-/-) mice after lung E. coli infection. In contrast, GV(+/+) mice have higher levels of prostaglandin D(2) (PGD(2)), PGF(2α), and 15-keto-PGE(2) in lung and express higher levels of ICAM-1 and PECAM-1 on pulmonary endothelial cells than GV(-/-) mice after lung infection with E. coli. Selective deletion of GV sPLA(2) in non-myeloid cells impairs leukocyte accumulation after pulmonary E. coli infection, and lack of GV sPLA(2) in either bone marrow-derived myeloid cells or non-myeloid cells attenuates E. coli clearance from the alveolar space and the lung parenchyma. These observations show that GV sPLA(2) in bone marrow-derived myeloid cells as well as non-myeloid cells, which are likely bronchial epithelial cells, participate in the regulation of the innate immune response to pulmonary infection with E. coli.
authors.affiliation: Division of Vascular Surgery, Peter Munk Cardiac Centre, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Norbert
authors.initials: N
authors.lastname: Degousee
authors.affiliation: Division of Experimental Therapeutics, University of Toronto, Toronto, Ontario M5G 2C4, Canada; Division of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, People's Republic of China.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kelvin
authors.affiliation: Institut für Klinische Pharmakologie, D-60590, Frankfurt am Main, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.affiliation: Department of Pathology, Toronto General Hospital Research Institute of the University Health Network and the Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Hwang
authors.affiliation: Division of Vascular Surgery, Peter Munk Cardiac Centre, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Eva
authors.initials: E
authors.lastname: Stefanski
authors.affiliation: Department of Medical Oncology and Hematology, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Division of Experimental Therapeutics, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Danesh
authors.affiliation: Institut für Klinische Pharmakologie, D-60590, Frankfurt am Main, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Angioni
authors.affiliation: Institut für Klinische Pharmakologie, D-60590, Frankfurt am Main, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Division of Vascular Surgery, Peter Munk Cardiac Centre, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lindsay
authors.affiliation: Departments of Chemistry and Biochemistry, University of Washington, Seattle, Washington 98195.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.affiliation: Departments of Chemistry and Biochemistry, University of Washington, Seattle, Washington 98195.
authors.forename: James
authors.initials: J
authors.lastname: Bollinger
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice, Sophia Antipolis et Centre National de la Recherche Scientifique, Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Payré
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice, Sophia Antipolis et Centre National de la Recherche Scientifique, Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lambeau
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, and Partners Asthma Center, Brigham and Women's Hospital, Boston Massachusetts 02115.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Arm
authors.affiliation: Department of Medical Oncology and Hematology, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Armand
authors.initials: A
authors.lastname: Keating
authors.affiliation: Division of Vascular Surgery, Peter Munk Cardiac Centre, University of Toronto, Toronto, Ontario M5G 2C4, Canada. Electronic address: barry.rubin@uhn.on.ca.
authors.forename: Barry B
authors.initials: BB
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D018893:Bronchoalveolar Lavage; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D004926:Escherichia coli / Q000276:immunology* / Q000378:metabolism; D004927:Escherichia coli Infections / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D054505:Group V Phospholipases A2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006868:Hydrolysis; D007113:Immunity, Innate; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015230:Prostaglandin D2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000201:enzymology / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D054505:Group V Phospholipases A2; D015230:Prostaglandin D2