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Papers In Press, published online ahead of print November 7, 2006
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Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871
Corresponding Author: koseki{at}imed2.med.osaka-u.ac.jp
Lipid rafts on the cell surface are believed to be very important as platforms for various cellular functions. The aim of the present study was to know whether defective lipid efflux may influence lipid rafts on the cell surface and their related cellular functions. We investigated macrophages (M
Revised on October 31, 2006
Accepted on November 1, 2006
Increased lipid rafts and accelerated lipopolysaccharide-induced tumor necrosis factor
secretion in Abca1-deficient macrophages
s) with defective lipid efflux from ATP-binding cassette transporter-A1 (Abca1)-deficient mice. Lipid rafts were evaluated by the following two novel probes: a protease-nicked and biotinylated derivative of perfringolysin O (BC
) and a fluorescein ester of polyethylene glycol-derived cholesterol (fPEG-chol). Lipid rafts in Abca1-deficient (Abca1-KO) M
s were increased, as demonstrated by both probes. Moreover, activities of nuclear factor-kappa B (NF
B), mRNA and intracellular distribution, and secretion of tumor necrosis factor
(TNF
) were examined following the stimulation by lipopolysaccharides (LPS). LPS-induced responses of activation of NF-
B and TNF
were more prompt and accelerated in the Abca1-KO M
s, compared with wild type M
s. Modification of lipid rafts by cyclodextrin and nystatin corrected the abnormal response, suggesting an association between the increased lipid rafts and abnormal TNF
secretion. We report here Abca1-KO M
s with defective lipid efflux exhibited the increased lipid rafts on the cell surface and the accelerated TNF
secretion.
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