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Lipopolysaccharide induces distinct alterations in the microtubule cytoskeleton of monocytes

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Abstract

Microtubules are obligate functional elements of almost all eukaryotic cells. They are involved in a broad range of essential cellular functions and structural changes of this system may trigger cell death. Recently, we have reported that lipopolysaccharides inhibitin vitro microtubule formation due to exclusion of microtubule-associated proteins. The distinct epitopes of lipopolysaccharides responsible for these effects and thein vivo relevance of these data are unknown. Therefore, this study was conducted to elucidate the effects of lipid A, the biologically active motif of lipopolysaccharides, on microtubule formationin vitro and to prove whether lipopolysaccharides affect the microtubule architecture of cultured human monocytesin vivo. Despite a dose- and pH-dependent inhibition of microtubule formation by lipopolysaccharides, inhibition of microtubule assembly could be mimicked by lipid A. Near-infrared two-photon microscopy revealed that human peripheral blood monocytes accumulate lipopolysaccharides. A vesicular distribution pattern of lipopolysaccharides within the monocytes was observed. Confocal laser scanning microscopy demonstrated alterations in the microtubule architecture of monocytes after incubation with lipopolysaccharides. Lipid A seems to be responsible for the observed crosstalk between lipopolysaccharides and microtubule proteins. Furthermore, our data indicate that lipopolysaccharides may affect the microtubule architecture in human monocytes after intracellular accumulation directly. Therefore, we conclude, that the microtubule cytoskeleton is an essential intracellular target for sepsis-relevant bacterial components such as lipopolysaccharides.

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Authors and Affiliations

  1. Department of Anaesthesiology and Critical Care Medicine, University of Jena, Jena, Germany

    S. Rußwurm, M. Wiederhold & K. Reinhart

  2. Institute of Molecular Biotechnology, University of Jena, Jena, Germany

    K.J. Böhm & P. Mühlig

  3. Institute of Anatomy II, University of Jena, Jena, Germany

    K. König

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  1. S. Rußwurm
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  2. K.J. Böhm
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  3. P. Mühlig
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  4. M. Wiederhold
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  5. K. König
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  6. K. Reinhart
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Rußwurm, S., Böhm, K., Mühlig, P. et al. Lipopolysaccharide induces distinct alterations in the microtubule cytoskeleton of monocytes. Cell Biol Toxicol 16, 339–346 (2000). https://doi.org/10.1023/A:1026754631964

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