Resolvin E1 modulates Mac-1 signaling and promotes neutrophil apoptosis and the resolution of acute inflammation (P5064)
Bibliographic record
Abstract
Abstract Resolvin E1 (RvE1), derived from the omega-3 polyunsaturated fatty acid eicosapentaenoic acid inhibits Mac-1 (CD11b/CD18)-mediated neutrophil trafficking. Mac-1also generates ligand-specific outside-in signals to modulate neutrophil apoptosis, a critical control point in the resolution of inflammation. We studied the impact of RvE1 on Mac-1signaling and neutrophil apoptosis. Culture of human neutrophils with RvE1 (0.1-10 nM) mitigated ERK and Akt-mediated survival signals from the Mac-1 ligand myeloperoxidase, leading to Mcl-1 degradation and mitochondrial dysfunction. RvE1 facilitated phagocytosis of C3b-opsonized E. coli and triggered phagocytosis-induced apoptosis. RvE1 through the leukotriene B4 receptor BLT1 evoked ROS generation by NADPH oxidase, leading to activation of caspase-8 and 3. In mice, treatment with RvE1 at the peak of inflammation enhanced the resolution of E. coli pneumonia, E. coli peritonitis-associated and carrageenan plus myeloperoxidase-evoked neutrophil-mediated lung injury through facilitating neutrophil apoptosis and removal of apoptotic neutrophils by macrophages. These actions of RvE1 were prevented by the pan-caspase inhibitor zVAD-fmk. Our results identify a novel resolution circuit, in which RvE1 through BLT1 shifts the balance between Mac-1-generated competing pro- and anti-apoptotic signals toward apoptotic pathways, and consequently enhances resolution of acute lung inflammation.
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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 | 0.001 |
| 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".