title: Pulmonary surfactant phosphatidylglycerol inhibits Mycoplasma pneumoniae-stimulated eicosanoid production from human and mouse macrophages.
abstract: Mycoplasma pneumoniae is a human pathogen causing respiratory infections that are also associated with serious exacerbations of chronic lung diseases. Membranes and lipoproteins from M. pneumoniae induced a 4-fold increase in arachidonic acid (AA) release from RAW264.7 and a 2-fold increase in AA release from primary human alveolar macrophages. The bacterial lipoprotein mimic and TLR2/1 agonist Pam3Cys and the TLR2/6 agonist MALP-2 produced effects similar to those elicited by M. pneumoniae in macrophages by inducing the phosphorylation of p38(MAPK) and p44/42(ERK1/2) MAP kinases and cyclooxygenase-2 (COX-2) expression. M. pneumoniae induced the generation of prostaglandins PGD(2) and PGE(2) from RAW264.7 cells and thromboxane B(2) (TXB(2)) from human alveolar macrophages. Anti-TLR2 antibody completely abolished M. pneumoniae-induced AA release and TNFα secretion from RAW264.7 cells and human alveolar macrophages. Disruption of the phosphorylation of p44/42(ERK1/2) or inactivation of cytosolic phospholipase A(2)α (cPLA(2)α) completely inhibited M. pneumoniae-induced AA release from macrophages. The minor pulmonary surfactant phospholipid, palmitoyl-oleoyl-phosphatidylglycerol (POPG), antagonized the proinflammatory actions of M. pneumoniae, Pam3Cys, and MALP-2 by reducing the production of AA metabolites from macrophages. The effect of POPG was specific, insofar as saturated PG, and saturated and unsaturated phosphatidylcholines did not have significant effect on M. pneumoniae-induced AA release. Collectively, these data demonstrate that M. pneumoniae stimulates the production of eicosanoids from macrophages through TLR2, and POPG suppresses this pathogen-induced response.
authors.affiliation: From the Departments of Medicine and.
authors.forename: Pitchaimani
authors.initials: P
authors.lastname: Kandasamy
authors.affiliation: the Department of Pharmacology, University of Colorado Denver School of Medicine, Aurora, Colorado 80011.
authors.forename: Simona
authors.initials: S
authors.lastname: Zarini
authors.affiliation: From the Departments of Medicine and.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Chan
authors.affiliation: the Department of Pharmacology, University of Colorado Denver School of Medicine, Aurora, Colorado 80011; Pediatrics, National Jewish Health, Denver, Colorado, 80206 and.
authors.forename: Christina C
authors.initials: CC
authors.lastname: Leslie
authors.affiliation: the Department of Pharmacology, University of Colorado Denver School of Medicine, Aurora, Colorado 80011.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Murphy
authors.affiliation: From the Departments of Medicine and. Electronic address: voelkerd@njhealth.org.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000276:immunology / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D015777:Eicosanoids / Q000276:immunology / Q000378:metabolism*; D054513:Group IV Phospholipases A2 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology; D008074:Lipoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000276:immunology / Q000378:metabolism; D009177:Mycoplasma pneumoniae / Q000276:immunology / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D011019:Pneumonia, Mycoplasma / Q000276:immunology / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015777:Eicosanoids; D055666:Lipopeptides; D008074:Lipoproteins; D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C069172:2,3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine; C106335:macrophage stimulatory lipopeptide 2; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D054513:Group IV Phospholipases A2; C516389:PLA2G4A protein, human; D003545:Cysteine