Abstract
Abstract Mycoplasmas and their membranes are potent activators of macrophages, the active principle being lipoproteins and lipopeptides. Two stereoisomers of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 (MALP-2) differing in the configuration of the lipid moiety were synthesized and compared in their macrophage-activating potential, the R-MALP being >100 times more active than the S-MALP in stimulating the release of cytokines, chemokines, and NO. To assess the role of the Toll-like receptor (TLR) family in mycoplasmal lipopeptide signaling, the MALP-2-mediated responses were analyzed using macrophages from wild-type, TLR2-, TLR4-, and MyD88-deficient mice. TLR2- and MyD88-deficient cells showed severely impaired cytokine productions in response to R- and S-MALP. The MALP-induced activation of intracellular signaling molecules was fully dependent on both TLR2 and MyD88. There was a strong preference for the R-MALP in the recognition by its functional receptor, TLR2.
Keywords
LipopeptideTLR2Cell biologyToll-like receptorReceptorSignal transductionChemokineMacrophageIntracellularBiologyChemistryTLR4Innate immune systemBiochemistryBacteriaIn vitro
MeSH Terms
Adaptor ProteinsSignal TransducingAnimalsAntigensDifferentiationCellsCulturedDrosophila ProteinsLipopeptidesLipoproteinsMacrophage ActivationMacrophagesPeritonealMembrane GlycoproteinsMiceMiceInbred C3HMiceInbred C57BLMiceKnockoutMycoplasma fermentansMyeloid Differentiation Factor 88OligopeptidesReceptorsCell SurfaceReceptorsImmunologicSignal TransductionStereoisomerismStructure-Activity RelationshipToll-Like Receptor 2Toll-Like Receptor 4Toll-Like Receptors
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Publication Info
- Year
- 2000
- Type
- article
- Volume
- 164
- Issue
- 2
- Pages
- 554-557
- Citations
- 571
- Access
- Closed
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Cite This
Osamu Takeuchi,
Andreas M. Kaufmann,
Karsten Grote
et al.
(2000).
Cutting Edge: Preferentially the <i>R</i>-Stereoisomer of the Mycoplasmal Lipopeptide Macrophage-Activating Lipopeptide-2 Activates Immune Cells Through a Toll-Like Receptor 2- and MyD88-Dependent Signaling Pathway.
The Journal of Immunology
, 164
(2)
, 554-557.
https://doi.org/10.4049/jimmunol.164.2.554
Identifiers
- DOI
- 10.4049/jimmunol.164.2.554
- PMID
- 10623793