Essential role of albumin in CD14-independent activation of MD-2/TLR4 by endotoxin (135.20)
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".