Akihito Nishiyama, Hirokazu Isobe, Yasuhisa Iwao, Tomomi Takano, Wei-Chun Hung, Ikue Taneike, Saori Nakagawa, Soshi Dohmae, Nobuhiro Iwakura, Tatsuo Yamamoto
Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
FEMS immunology and medical microbiology 2012 DecThe mechanisms for the cytotoxicity of staphylococcal Panton-Valentine leukocidin (PVL), a pore-forming toxin consisting of LukS-PV and LukF-PV, in human immune cells are still unclear. Because LukS-PV binds to ganglioside GM1, a constituent of detergent-resistant membrane microdomains (DRMs) of the plasma membrane, the role of DRMs in PVL cytotoxicity was examined in human polymorphonuclear neutrophils (PMNs), monocytes, HL-60 cells, and THP-1 cells. PVL binding capacities in HL-60 and THP-1 cells were higher than those in PMNs and monocytes; however, the PVL concentration to obtain more than 80% cell lysis in HL-60 cells was 10 times higher than that in PMNs and PVL even at such concentration induced < 10% cell lysis in THP-1 cells. After incubation of PMNs with LukS-PV, more than 90% of LukS-PV bound to the detergent-soluble membranes. Subsequent incubation with LukF-PV at 4 °C induced the accumulation of more than 70% of PVL components and 170- to 220-kDa complex formation in DRMs in an actin-independent manner. However, only 30% of PVL was found, and complex formation was under detectable level in DRMs in HL-60 cells. PVL did not accumulate in DRMs in THP-1 cells. Our observations strongly indicate that PVL accumulation in DRMs is essential for PVL cytotoxicity. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
Akihito Nishiyama, Hirokazu Isobe, Yasuhisa Iwao, Tomomi Takano, Wei-Chun Hung, Ikue Taneike, Saori Nakagawa, Soshi Dohmae, Nobuhiro Iwakura, Tatsuo Yamamoto. Accumulation of staphylococcal Panton-Valentine leukocidin in the detergent-resistant membrane microdomains on the target cells is essential for its cytotoxicity. FEMS immunology and medical microbiology. 2012 Dec;66(3):343-52
PMID: 22924956
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