title: The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone stimulates phagocytic activity in human macrophages through the p38 MAPK pathway.
abstract: Quorum-sensing is an important mechanism for the regulation of bacteria-to-bacteria communication. Recent advances have demonstrated that the Pseudomonas aeruginosa signaling molecule N-(3-oxododecanoyl)-L-homoserine lactone (3O-C(12)-HSL) is also a potent modulator of eukaryotic cells and may thus play an important role in the host response during P. aeruginosa infections. Little is known, however, about specific effects of 3O-C(12)-HSL molecules on human macrophages. To address this issue, we investigated the influence of 3O-C(12)-HSL on the phagocytic activity, production of reactive oxygen species, and activation of p38 and p42/44 MAPK signaling pathways in human macrophages. We show an effect of 3O-C(12)-HSL on the phagocytic capacity in human macrophages, which depends on concentration and time of exposure. When cells were exposed to 100 microM 3O-C(12)-HSL for 30 min or 1 h, the phagocytic activity increased 1.8 and 1.6 times, respectively. The 3O-C(12)-HSL treatments had no significant effect on the level of reactive oxygen species production. Furthermore, the p38 MAPK, but not the p42/44 MAPK, signaling pathway was activated in response to 3O-C(12)-HSL. In addition, specific blocking of p38 MAPK activation with 10 microM SB 203580 prevented the 3O-C(12)-HSL-induced increase in the phagocytic activity. These findings demonstrate that the bacterial quorum-sensing can play a significant role also in regulation of macrophage activity during infections caused by P. aeruginosa.
authors.affiliation: Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Linköping University, SE-58185, Sweden. elevi@imk.liu.se
authors.forename: Elena
authors.initials: E
authors.lastname: Vikström
authors.forename: Karl-Eric
authors.initials: KE
authors.lastname: Magnusson
authors.forename: Augustas
authors.initials: A
authors.lastname: Pivoriūnas
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006714:Homoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007155:Immunologic Factors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D007155:Immunologic Factors; C109860:N-(3-oxododecanoyl)homoserine lactone; D017382:Reactive Oxygen Species; D006714:Homoserine; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; D015107:4-Butyrolactone