title: Direct stimulatory effects of the TLR2/6 ligand bacterial lipopeptide MALP-2 on neutrophil granulocytes.
abstract: Bacterial lipopeptides represent a group of bacterial compounds able to trigger the functions of cells of the innate immune response. Whereas diacylated lipopeptides are recognized by TLR2/6 dimers, triacylated lipopeptides were shown to act via TLR2/1 dimers. Although several previous studies dealt with the effect of the TLR2/1 ligand Pam(3)CysSK(4) on neutrophil granulocytes (PMN), it is still not clear whether TLR2/6 ligand lipopeptides can directly influence PMN functions. In the present study we used highly purified human neutrophils to investigate the direct effects of the diacylated mycoplasmal macrophage activating lipopeptide-2 (MALP-2) on the function of neutrophil granulocytes. After exposure to 10 ng/ml MALP-2 neutrophils acquired activated cell shape, secreted IL-8 and MIP-1beta and their phagocytic capacity was enhanced. Analysis of cell surface activation markers confirmed the activating effect of MALP-2, the expression of CD62L was downregulated whereas CD11b was upregulated on PMN after exposure to MALP-2. The constitutive apoptosis of PMN was inhibited after exposure to MALP-2. However, MALP-2 exerted only a short-term effect on the apoptosis of resting neutrophils, a longer lasting effect was observed after transendothelial migration. MALP-2 did not directly induce the production of reactive oxygen intermediates but primed PMN for a fMLP-induced oxidative burst. The migration of neutrophils was enhanced after treatment with MALP-2. This was due, however, to a chemokinetic rather than to a chemotactic effect. Pam(3)CysSK(4) also activated PMN, but in comparison to MALP-2, at higher concentrations. These findings suggest that diacylated lipopeptides are important microbial structures recognized by and acting on neutrophil granulocytes.
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Luebeck, Ratzeburger Allee 160, 23538 Lubeck, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Wilde
authors.forename: Sonja
authors.initials: S
authors.lastname: Lotz
authors.forename: David
authors.initials: D
authors.lastname: Engelmann
authors.forename: Andrea
authors.initials: A
authors.lastname: Starke
authors.forename: Ger
authors.initials: G
authors.lastname: van Zandbergen
authors.forename: Werner
authors.initials: W
authors.lastname: Solbach
authors.forename: Tamás
authors.initials: T
authors.lastname: Laskay
mesh_terms: D017209:Apoptosis / Q000502:physiology; D016207:Cytokines / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D055666:Lipopeptides; D018375:Neutrophil Activation / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology; D016897:Respiratory Burst / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D055666:Lipopeptides; D009842:Oligopeptides; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; C106335:macrophage stimulatory lipopeptide 2