Extracellular nucleotides mediate LPS‐induced IL‐8 release from monocytes and neutrophil migration.
Bibliographic record
Abstract
Extracellular nucleotides are released from activated, damaged or dead cells and drive inflammation by the stimulation of P2 receptors. We previously reported that the gram‐negative bacteria pathogen, LPS, released IL‐8 from monocytic THP‐1 cells via the activation of P2Y 6 receptor. In extension of this study, we now demonstrate that primary human monocytes treated with LPS or UDP also release IL‐8 and that this secretion mediates neutrophil migration. Importantly, the LPS‐induced IL‐8 release was blocked by a nucleotide scavenger (apyrase) and this blockage was not due to the formation of adenosine. We next tested the chemotactic activity of conditioned monocyte media on neutrophil migration using Boyden chambers with endothelial monolayers. The media of LPS‐stimulated monocytes recruited significantly more neutrophils than the corresponding media to which LPS was added simultaneously with apyrase. Conditioned media of UDP‐stimulated monocytes were as effective to induce neutrophil migration. In addition, IL‐8 neutralizing antibodies added to the media of LPS‐ or UDP‐treated monocytes almost completely abrogated their chemotactic activity. Therefore, extracellular nucleotides have the ability to recruit neutrophils to inflamed tissues by mediating IL‐8 release from human monocytes/macrophages. Supported by grants from the CIHR and The Arthritis Society.
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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) | 0.002 | 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".