title: Bacterial quorum sensing molecule induces chemotaxis of human neutrophils via induction of p38 and leukocyte specific protein 1 (LSP1).
abstract: When bacteria colonize surfaces, they socialize and form biofilms. This process is well regulated and relies on the communication among the bacteria via so-called "quorum sensing molecules". Among those, N-(3-oxododecanoyl)-L-homoserine lactone (AHL-12), generated by Pseudomonas aeruginosa and other Gram-negative bacteria, activates not only bacteria but also interacts with mammalian cells. Among others, it activates phagocytic cells and - as we had shown previously - it is chemotactic for human polymorphonuclear neutrophils (PMN) in vitro. In the present study, we analyzed the signalling pathway of AHL-12 in PMN. We focused on the mitogen activated protein (MAP) kinase p38, because SB203580, an inhibitor of p38, prevented the AHL-12 induced chemotaxis. We found that in response to AHL-12, p38 was phosphorylated within minutes, as was its downstream target, the MAPKAP-Kinase-2 (MK2). In PMN, the major substrate of MK2 is the leukocyte specific protein 1 (LSP1), which binds to F-actin and participates directly in actin polymerization and cell migration. In response to AHL-12, LSP1 was phosphorylated and co-localized with F-actin in polarized PMN, suggesting that AHL-12-induced migration depended on p38 and LSP1 activation.
authors.affiliation: Institut für Immunologie der Universität Heidelberg, Heidelberg, Germany. Nadine.Kahle@immu.uni-heidelberg.de
authors.forename: N A
authors.initials: NA
authors.lastname: Kahle
authors.forename: G
authors.initials: G
authors.lastname: Brenner-Weiss
authors.forename: J
authors.initials: J
authors.lastname: Overhage
authors.forename: U
authors.initials: U
authors.lastname: Obst
authors.forename: G M
authors.initials: GM
authors.lastname: Hänsch
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008840:Microfilament Proteins / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011725:Pyridines / Q000494:pharmacology; D053038:Quorum Sensing; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D015107:4-Butyrolactone; D000199:Actins; D006714:Homoserine; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C489183:LSP1 protein, human; C109860:N-(3-oxododecanoyl)homoserine lactone; C093642:SB 203580