Lipopolysaccharide induces distinct alterations in the microtubule cytoskeleton of monocytes

Microtubules are obligate functional elements of almost all eukaryotic cell s. They are involved in a broad range of essential cellular functions and s tructural changes of this system may trigger cell death. Recently, we have reported that lipopolysaccharides inhibit in vitro microtubule formation du e to exclusion of microtubule-associated proteins. The distinct epitopes of lipopolysaccharides responsible for these effects and the in vivo relevanc e of these data are unknown. Therefore, this study was conducted to elucida te the effects of lipid A, the biologically active motif of lipopolysacchar ides, on microtubule formation in vitro and to prove whether lipopolysaccha rides affect the microtubule architecture of cultured human monocytes in vi vo. 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 periphe ral blood monocytes accumulate lipopolysaccharides. A vesicular distributio n pattern of lipopolysaccharides within the monocytes was observed. Confoca l laser scanning microscopy demonstrated alterations in the microtubule arc hitecture of monocytes after incubation with lipopolysaccharides. Lipid A s eems to be responsible for the observed crosstalk between lipopolysaccharid es and microtubule proteins. Furthermore, our data indicate that lipopolysa ccharides may affect the microtubule architecture in human monocytes after intracellular accumulation directly. Therefore, we conclude, that the micro tubule cytoskeleton is an essential intracellular target for sepsis-relevan t bacterial components such as lipopolysaccharides.