Membrane fluidity matters: hyperthermia from the aspects of lipids and membranes.

Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity. However, further increasing membrane fluidity to sensitise to chemo- or radiotherapy could have some other effects. In fact, hyperfluidisation of cell membrane induced by membrane fluidiser initiates a stress response as the heat shock protein response, which may modulate positively or negatively apoptotic cell death. Overviewing some recent findings based on a technology allowing direct imaging of lipid rafts in live cells and lipidomics, novel aspects of the intimate relationship between the 'membrane stress' of tumour cells and the cellular heat shock response will be highlighted. Our findings lend support to both the importance of membrane remodelling and the release of lipid signals initiating stress protein response, which can operate in tandem to control the extent of the ultimate cellular thermosensitivity. Overall, we suggest that the fluidity variable of membranes should be used as an independent factor for predicting the efficacy of combinational cancer therapies.

The role of lipopolysaccharide moieties in macrophage response to Escherichia coli.

Lipopolysaccharide (LPS) is the main component of Gram-negative bacteria that - upon infection - activates the host immune system and is crucial in fighting pathogens as well as in the induction of sepsis. In the present study we addressed the question whether the key structural components of LPS equally take part in the activation of different macrophage immune responses. By genomic modifications of Escherichia coli MG1655, we constructed a series of strains harboring complete and truncated forms of LPS in their cell wall. These strains were exposed to RAW 264.7 macrophages, after which phagocytosis, fast release of pre-synthesized TNF and activation of NF-kappaB signal transduction pathway were quantified. According to our results the core and lipid A moieties are involved in immune recognition. The most ancient part, lipid A is crucial in evoking immediate TNF release and activation of NF-kappaB. The O-antigen inhibits phagocytosis, leading to immune evasion.