The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Isolation of an endotoxin–MD-2 complex that produces Toll-like receptor 4-dependent cell activation at picomolar concentrations
Open accessAbstract
Host proinflammatory responses to minute amounts of endotoxins derived from many Gram-negative bacteria require the interaction of lipopolysaccharide-binding protein (LBP), CD14, Toll-like receptor 4 (TLR4) and MD-2. Optimal sensitivity to endotoxin requires an ordered series of endotoxin–protein and protein–protein interactions. At substoichiometric concentrations, LBP facilitates delivery of endotoxin aggregates to soluble CD14 (sCD14) to form monomeric endotoxin–sCD14 complexes. Subsequent interactions of endotoxin–sCD14 with TLR4 and/or MD-2 have not been specifically defined. This study reports the purification of a stable, monomeric, bioactive endotoxin–MD-2 complex generated by treatment of endotoxin–sCD14 with recombinant MD-2. Efficient generation of this complex occurred at picomolar concentrations of endotoxin and nanogram per milliliter doses of MD-2 and required presentation of endotoxin to MD-2 as a monomeric endotoxin–CD14 complex. TLR4-dependent delivery of endotoxin to human embryonic kidney (HEK) cells and cell activation at picomolar concentrations of endotoxin occurred with the purified endotoxin–MD-2 complex, but not with purified endotoxin aggregates with or without LBP and/or sCD14. The presence of excess MD-2 inhibited delivery of endotoxin–MD-2 to HEK/TLR4 cells and cell activation. These findings demonstrate that TLR4-dependent activation of host cells by picomolar concentrations of endotoxin occurs by sequential interaction and transfer of endotoxin to LBP, CD14, and MD-2 and simultaneous engagement of endotoxin and TLR4 by MD-2.
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Cites
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Lipopolysaccharide Interaction with Cell Surface Toll-like Receptor 4-MD-2
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Cited by
LPS/TLR4 signal transduction pathway
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Toll-like Receptors and the Control of Immunity
Fitzgerald, K. A., & Kagan, J. C. (2020) · Cell · doi:10.1016/j.cell.2020.02.041 · Cited by 2,168
CD14 Controls the LPS-Induced Endocytosis of Toll-like Receptor 4
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Assembly and localization of Toll-like receptor signalling complexes
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Decoding Toll-like receptors: Recent insights and perspectives in innate immunity
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Metadata
- Authors
- Gioannini, T. L., Teghanemt, A., Zhang, D., Coussens, N. P., Dockstader, W., Ramaswamy, S., & Weiss, J. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-03-09
- Volume
- 101
- Issue
- 12
- Pages
- 4186-4191
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2068365384
- Cited by
- 366
- References
- 41
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- green
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- Gioannini, T. L., Teghanemt, A., Zhang, D., Coussens, N. P., Dockstader, W., Ramaswamy, S., & Weiss, J. P. (2004). Isolation of an endotoxin–MD-2 complex that produces Toll-like receptor 4-dependent cell activation at picomolar concentrations. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0306906101
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