Concomitant activation of P2Y<sub>2</sub> and P2Y<sub>6</sub> receptors on monocytes is required for TLR1/2‐induced neutrophil migration by regulating IL‐8 secretion
Bibliographic record
Abstract
Extracellular nucleotides regulate a variety of cellular responses involved in inflammation via the activation of P2 receptors. Here, we show that nucleotides regulate TLR2-induced neutrophil migration both in vivo and in vitro. The nucleotide scavenger apyrase inhibited neutrophil recruitment in murine air pouches injected with the TLR2 agonist Pam(3)CSK(4). In agreement, the supernatants of either human primary monocytes or monocytic cells (THP-1 and U937) treated with Pam(3)CSK(4) recruited significantly fewer neutrophils when the former cells were treated in the presence of apyrase. As demonstrated with inhibitory Ab, these supernatants induced neutrophil migration due to IL-8 secretion. In addition, IL-8 secretion was markedly diminished by the non-selective P2 receptor antagonists reactive blue 2 and suramin, and by a selective P2Y(6) antagonist, MRS2578. Selective antagonists of P2Y(1) (MRS2500) and P2Y(11) (NF157) did not affect IL-8 release. The knockdown of either P2Y(2) or P2Y(6) with specific shRNA diminished IL-8 secretion from Pam(3)CSK(4)-treated THP-1 cells. Altogether, these results show that extracellular nucleotides, via P2Y(2) and P2Y(6) receptors, regulate neutrophil migration by controlling TLR2-induced IL-8 release from human monocytes. In line with our previous work on TLR4, this study further supports the importance of nucleotides in bacterial-induced neutrophil migration.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".