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1: Med Microbiol Immunol. 2007 Jun;196(2):61-71. Epub 2006 Sep 28.
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Direct stimulatory effects of the TLR2/6 ligand bacterial lipopeptide MALP-2 on neutrophil granulocytes.

Wilde I, Lotz S, Engelmann D, Starke A, van Zandbergen G, Solbach W, Laskay T.

Institute of Medical Microbiology and Hygiene, University of Luebeck, Ratzeburger Allee 160, 23538 Lubeck, Germany.

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.

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PMID: 17006695 [PubMed - indexed for MEDLINE]