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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow Cells / enzymology
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Bone Marrow Cells / immunology*
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Bone Marrow Cells / pathology
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Bronchi / enzymology
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Bronchi / immunology*
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Bronchi / pathology
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Bronchoalveolar Lavage
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Cytokines / genetics
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Cytokines / immunology
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Cytokines / metabolism
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Epithelial Cells / enzymology
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Epithelial Cells / immunology*
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Epithelial Cells / pathology
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Escherichia coli / immunology*
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Escherichia coli / metabolism
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Escherichia coli Infections / enzymology
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Escherichia coli Infections / genetics
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Escherichia coli Infections / immunology*
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Escherichia coli Infections / pathology
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Group V Phospholipases A2 / genetics
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Group V Phospholipases A2 / immunology*
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Group V Phospholipases A2 / metabolism
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Hydrolysis
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Immunity, Innate*
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / immunology
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Intercellular Adhesion Molecule-1 / metabolism
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Mice
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Mice, Knockout
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Myeloid Cells / enzymology
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Myeloid Cells / immunology*
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Myeloid Cells / pathology
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Platelet Endothelial Cell Adhesion Molecule-1 / genetics
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Platelet Endothelial Cell Adhesion Molecule-1 / immunology
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Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
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Pneumonia, Bacterial / enzymology
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Pneumonia, Bacterial / genetics
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Pneumonia, Bacterial / immunology*
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Pneumonia, Bacterial / pathology
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Prostaglandin D2 / genetics
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Prostaglandin D2 / immunology
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Prostaglandin D2 / metabolism
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Pulmonary Alveoli / enzymology
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Pulmonary Alveoli / immunology
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Pulmonary Alveoli / pathology
Substances
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Cytokines
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Platelet Endothelial Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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Group V Phospholipases A2
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Prostaglandin D2