title: Lipid body mobilization in the ExoU-induced release of inflammatory mediators by airway epithelial cells.
abstract: This report addressed the question whether ExoU stimulation of airway epithelial cells may contribute to the inflammatory response detected in the course of Pseudomonas aeruginosa respiratory infections. Infection with PA103 P. aeruginosa elicited a potent release of IL-6 and IL-8, as well as of arachidonic acid (AA) and PGE(2) that was reduced by the bacterial treatment with MAFP, a cPLA(2) inhibitor. Airway cells from the BEAS-2B line and in primary culture were shown to be enriched in lipid bodies (LBs), that are cytoplasmic domains implicated in AA transformation into eicosanoids. However, cells infected with PA103 and with a mutant deficient in exoU but complemented with a functional gene exhibited reduced contents of LBs, and this reduction was inhibited by MAFP. FACS analysis showed that the decrease in the LB content correlated with the presence of intracellular PGE(2). Also, in PA103-infected cells, PGE(2) was immunolocalized in LBs, suggesting that the reduction in the cell content of the organelles was due to consumption of their glycerolipids, resulting in local synthesis of the prostanoid. In conclusion, we showed the ExoU ability to induce airway epithelial cells to overproduce PGE(2) and we speculate that LB may represent intracellular loci involved in ExoU-induced eicosanoid synthesis.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Avenue 28 de Setembro, 87 Fundos, 3o andar, 20 551-030, Rio de Janeiro, Brazil. crisplot@yahoo.com.br
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Plotkowski
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Brandão
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: de Assis
authors.forename: Luis-Filipe P
authors.initials: LF
authors.lastname: Feliciano
authors.forename: Benoit
authors.initials: B
authors.lastname: Raymond
authors.forename: Carla
authors.initials: C
authors.lastname: Freitas
authors.forename: Alessandra M
authors.initials: AM
authors.lastname: Saliba
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Zahm
authors.forename: Lhousseine
authors.initials: L
authors.lastname: Touqui
authors.forename: Patrícia T
authors.initials: PT
authors.lastname: Bozza
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D050356:Lipid Metabolism; D063065:Organophosphonates / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism; D011552:Pseudomonas Infections / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D001426:Bacterial Proteins; D016207:Cytokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D063065:Organophosphonates; D011458:Prostaglandins E; C104810:methyl arachidonylfluorophosphonate; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa; D016718:Arachidonic Acid