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- W7480551 abstract "Abstract Host response to endotoxin (E) depends on the ordered interactions of LBP, CD14, MD-2 and Toll-Like Receptor (TLR) 4. CD14 is required for efficient transfer of E monomers to MD-2 (/TLR4) and for induction of TRIF-dependent signaling by activated TLR4. At high E concentrations, MD-2/TLR4-dependent cell activation by E is possible without CD14 through an unknown mechanism. We now show that incubation of purified E aggregates (Mr = 20 million) in PBS with = 0.1% albumin in the absence of the divalent cations Ca2+ and Mg2+, yields monomeric E:albumin complexes (Mr ~70,000). E monomers transfer from E:albumin to MD-2 and to MD-2/TLR4 directly and induce MD-2/TLR4-dependent, CD14-independent cell activation. Our findings suggest for the first time a mechanistic basis for CD14-independent cell activation by E. E:CD14 and E:albumin complexes should provide valuable reagents for future studies of MyD88-dependent (CD14-independent) and TRIF-dependent (CD14-dependent) TLR4 signaling by E. Work supported by NIH/NIAID #AI59372." @default.
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- W7480551 date "2009-04-01" @default.
- W7480551 modified "2023-09-25" @default.
- W7480551 title "Essential role of albumin in CD14-independent activation of MD-2/TLR4 by endotoxin (135.20)" @default.
- W7480551 doi "https://doi.org/10.4049/jimmunol.182.supp.135.20" @default.
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