Endotoxin·albumin complexes transfer endotoxin monomers to MD-2 resulting in activation of TLR4
| Autor: | Jerrold Weiss, DeSheng Zhang, Gregory A Esparza, Athmane Teghanemt, Theresa L. Gioannini |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
chemistry.chemical_classification
Lymphocyte antigen 96 biology Immunology Albumin Cell Biology Microbiology Divalent chemistry.chemical_compound Infectious Diseases Monomer chemistry Ectodomain Biochemistry biology.protein Biophysics Cell activation Receptor Molecular Biology Lipopolysaccharide binding protein |
| Zdroj: | Innate Immunity. 18:478-491 |
| ISSN: | 1753-4267 1753-4259 |
| DOI: | 10.1177/1753425911422723 |
| Popis: | Response to Gram-negative bacteria (GNB) is partially mediated by the recognition of GNB-derived endotoxin by host cells. Potent host response to endotoxin depends on the sequential interaction of endotoxin with lipopolysaccharide binding protein (LBP), CD14, MD-2 and TLR4. While CD14 facilitates the efficient transfer of endotoxin monomers to MD-2 and MD-2·TLR4, activation of MD-2·TLR4 can occur in the absence of CD14 through an unknown mechanism. Here, we show that incubation of purified endotoxin (E) aggregates (Eagg, M r ≥ 20 million) in PBS with ≥ 0.1% albumin in the absence of divalent cations Ca2+ and Mg2+, yields E·albumin complexes ( M r ∼70,000). E·albumin transfers E monomers to sMD-2 or sMD-2·TLR4 ectodomain (TLR4ecd) with a ‘ Kd’ of ∼4 nM and induces MD-2·TLR4-dependent, CD14-independent cell activation with a potency only 10-fold less than that of monomeric E·CD14 complexes. Our findings demonstrate, for the first time, a mechanistic basis for delivery of endotoxin monomers to MD-2 and for activation of TLR4 that is independent of CD14. |
| Databáze: | OpenAIRE |
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