De novo synthesis of proteinase 3 by cytokine primed circulating human polymorphonuclear neutrophils and mononuclear cells.
Bibliographic record
Abstract
OBJECTIVE: When polymorphonuclear neutrophils (PMN) and peripheral blood monocytes (PBMC) are stimulated with tumor necrosis factor alpha (TNF-alpha), preexisting granule stored proteinase 3 (PR3) is translocated to the surface of their plasma membrane. We investigated whether PR3 gene reactivation and new PR3 protein production were also features of priming by cytokine. METHODS: Normal human PMN and PBMC were isolated and stimulated in vitro with TNF-alpha. They were harvested at different intervals and subjected to total RNA and protein analysis. PR3 mRNA was identified by reverse transcription polymerase chain reaction, Northern blot, and sequencing. De novo PR3 synthesis was evaluated by metabolic labeling with [35S] methionine followed by immunoprecipitation using anti-neutrophil cytoplasmic antibodies from serum of patients with active Wegener's granulomatosis and mouse monoclonal anti-native PR3 antibodies. RESULTS: Resting PMN and PBMC do not express PR3 mRNA. During priming, PR3 mRNA appears in PMN at 2 h, peaks at 6 h, and has disappeared at 12 h. By comparison, in primed PBMC, PR3 mRNA appears at 6 h, peaks at 12 h, and disappears at 24 h. Immunoprecipitation of metabolically labeled PR3 revealed new synthesis of PR3 by both cell types, a process that was inhibited by cycloheximide. CONCLUSION: Primed PMN and PBMC can express PR3 mRNA and synthesize new PR3 protein, providing an alternative source to membrane PR3. Whether that small amount of inducible PR3 has a primary structure, a localization, or a role different from those of preformed PR3 stored in granules remains to be clarified.
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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) | 0.001 | 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".