Crystal‐induced neutrophil activation: VIII. Immediate production of prostaglandin E<sub>2</sub> mediated by constitutive cyclooxygenase 2 in human neutrophils stimulated by urate crystals
Bibliographic record
Abstract
OBJECTIVE: To evaluate the impact of monosodium urate monohydrate (MSUM) crystals on the synthesis of prostaglandin E(2) (PGE(2)) by human neutrophils, and to examine some of the mechanisms underlying these responses. METHODS: The amount of PGE(2) released in the supernatants of stimulated human neutrophils was evaluated by enzyme immunoassay, and expression of cyclooxygenase 2 (COX-2) was monitored by immunoblot on cell lysates, as well as by cytofluorometry of buffy-coat cells. RESULTS: We observed that MSUM crystals rapidly stimulated the synthesis of PGE(2), with levels peaking at 1 hour. This response was decreased by NS-398, a specific inhibitor of COX-2. We also detected a constitutive expression of COX-2 in unstimulated and unprimed neutrophils. This rapid COX-2-dependent PGE(2) accumulation was independent of translation and transcription. We also observed that piceatannol, but not colchicine, blocked the synthesis of PGE(2) stimulated by MSUM crystals. CONCLUSION: These results show that the interaction of MSUM crystals with human neutrophils stimulates a significant synthesis of PGE(2) mediated by constitutively expressed COX-2. The results of this study emphasize the potential importance of the neutrophil as a source of PGE(2), which may modulate, positively or negatively, the inflammatory response.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 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".