Leukotriene (LT) B4 metabolites inhibit the LTB4-mediated responses of human neutrophils.
Bibliographic record
Abstract
Abstract CONTEXT LTB4 is recognized as an excellent promoter of host defense. Indeed, it stimulates leukocyte functions mainly through the engagement of the BLT1 receptor. Of note, LTB4 induces phagocyte recruitment, the release of antimicrobial peptides, and potentiates the ingestion and the killing of pathogens. In humans, LTB4 has a short half-life and is rapidly metabolized into 12-oxo-LTB4 by monocytes/macrophages, or into 20-OH- and 20-COOH-LTB4 by neutrophils. Although LTB4 metabolites bind to the BLT1 receptor with high affinity, they poorly activate neutrophils. HYPOTHESIS We postulated that LTB4 metabolites might act as inhibitors of BLT1-mediated responses, therefore limiting the impact of LTB4 on human neutrophil functions and that inhibiting LTB4 degradation would enhance its effects on neutrophils. RESULTS 20-OH-, 20-COOH-, and 12-oxo-LTB4 inhibited all LTB4-mediated responses of neutrophils we tested (migration, degranulation, leukotriene biosynthesis). 20-OH-LTB4 was as efficient as the BLT1 antagonist CP 105,696 and all LTB4 metabolites were more potent than the anti-inflammatory and pro-resolving lipids resolvin E1 and 5(S),6(R)-lipoxin A4. In contrast, the fMLP- and IL-8-mediated responses were not affected by the LTB4 metabolites. Inhibiting LTB4 degradation into 20-OH-LTB4 in neutrophils notably amplified the LTB4-induced kinase phosphorylation and diminished the chemokinetic effect of LTB4. CONCLUSIONS Our data indicate that LTB4 metabolites act as natural inhibitors of LTB4-mediated responses and that preventing LTB4 metabolism can modulate some functions of neutrophils. These results support the idea that preventing LTB4 degradation might enhance host defense by boosting innate immunity.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".