1. Group V phospholipase A2 in bone marrow-derived myeloid cells and bronchial epithelial cells promotes bacterial clearance after Escherichia coli pneumonia
- Author
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David J. Kelvin, Carlo Angioni, Jonathan P. Arm, Eva Stefanski, Thomas F. Lindsay, Christine Payré, Helmut Schmidt, Barry B. Rubin, David M. Hwang, James G. Bollinger, Gérard Lambeau, Ali Danesh, Gerd Geisslinger, Norbert Degousee, Xing Hua Wang, Armand Keating, Michael H. Gelb, Division of Vascular Surgery, Peter Munk Cardiac Centre, University of Toronto, Division of Experimental Therapeutics, International Institute of Infection and Immunity, Shantou University Medical College, Institut für Klinische Pharmakologie, Department of Pathology, Department of Medical Oncology and Hematology, Departments of Chemistry and Biochemistry, University of Washington [Seattle], Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Division of Rheumatology, Immunology and Allergy and Partners Asthma Center, and Brigham and Women's Hospital [Boston]
- Subjects
MESH: Pulmonary Alveoli ,Biochemistry ,MESH: Mice, Knockout ,Bronchoalveolar Lavage ,Group V Phospholipases A2 ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,hemic and lymphatic diseases ,MESH: Animals ,Myeloid Cells ,Escherichia coli Infections ,Mice, Knockout ,0303 health sciences ,MESH: Cytokines ,medicine.diagnostic_test ,MESH: Bronchoalveolar Lavage ,MESH: Escherichia coli ,Prostaglandin D2 ,MESH: Bone Marrow Cells ,Hydrolysis ,MESH: Bronchi ,respiratory system ,Intercellular Adhesion Molecule-1 ,3. Good health ,Platelet Endothelial Cell Adhesion Molecule-1 ,medicine.anatomical_structure ,MESH: Epithelial Cells ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Cytokines ,MESH: Immunity, Innate ,lipids (amino acids, peptides, and proteins) ,MESH: Hydrolysis ,MESH: Pneumonia, Bacterial ,Immunology ,Prostaglandin ,Bone Marrow Cells ,Bronchi ,Biology ,Microbiology ,03 medical and health sciences ,Phospholipase A2 ,MESH: Group V Phospholipases A2 ,Parenchyma ,medicine ,Escherichia coli ,Pneumonia, Bacterial ,Animals ,Molecular Biology ,MESH: Mice ,030304 developmental biology ,MESH: Escherichia coli Infections ,Innate immune system ,Lung ,MESH: Intercellular Adhesion Molecule-1 ,MESH: Antigens, CD31 ,Epithelial Cells ,Cell Biology ,MESH: Myeloid Cells ,Immunity, Innate ,Pulmonary Alveoli ,MESH: Prostaglandin D2 ,Bronchoalveolar lavage ,chemistry ,Eicosanoid ,biology.protein ,Bone marrow ,030215 immunology - Abstract
International audience; 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.
- Published
- 2011
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