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 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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".