Innate Immunity | |
Endotoxin·albumin complexes transfer endotoxin monomers to MD-2 resulting in activation of TLR4: | |
Gregory AEsparza1  | |
关键词: Albumin; endotoxin; MD-2; Toll-like receptor 4; CD14; | |
DOI : 10.1177/1753425911422723 | |
学科分类:生物科学(综合) | |
来源: Sage Journals | |
【 摘 要 】
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, Mr ≥ 20 million) in PBS with ≥ 0.1% albumin in the absence of divalent cations Ca2+ and Mg2+, yields E·albumin complexes (Mr ∼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 activ...
【 授权许可】
CC BY
【 预 览 】
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RO201901224688148ZK.pdf | 717KB | download |