Accumulation of staphylococcal Panton-Valentine leukocidin in the detergent-resistant membrane microdomains on the target cells is essential for its cytotoxicity

作者：Nishiyama Akihito; Isobe Hirokazu; Iwao Yasuhisa; Takano Tomomi; Hung Wei Chun; Taneike Ikue; Nakagawa Saori; Dohmae Soshi; Iwakura Nobuhiro; Yamamoto Tatsuo^*

来源：FEMS Immunology and Medical Microbiology, 2012, 66(3): 343-352.

DOI：10.1111/j.1574-695X.2012.01027.x

• Panton-Valentine leukocidin
• community-acquired methicillin-resistant Staphylococcus aureus
• detergent-resistant membrane microdomains
• human polymorphonuclear neutrophils
• toxin accumulation
• cytotoxicity

The mechanisms for the cytotoxicity of staphylococcal PantonValentine 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 %26lt; 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 degrees 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.

• 出版日期2012-12