Suppressive effects of adenosine on the 5‐lipoxygenase pathway in human polymorphonuclear leukocytes
Bibliographic record
Abstract
Abstract Leukotrienes are potent mediators of inflammation and host defense. They are also involved in inflammatory and allergic diseases. While numerous studies have investigated the stimulatory mechanisms of leukotriene biosynthesis in phagocytes by inflammatory agents (chemoattractants, cytokines, etc.), the mechanisms responsible for the physiological downregulation of leukotriene biosynthesis have been the subject of very few investigations so far. It has, however, been reported that E‐type prostaglandins are potent inhibitors of leukotriene biosynthesis in chemoattractant‐stimulated neutrophils and we have recently shown with in vitro studies that endogenous adenosine is a potent inhibitor of leukotriene biosynthesis by neutrophils. The present review summarizes our studies demonstrating that adenosine downregulates leukotriene biosynthesis via an interaction with the adenosine A 2a receptor on neutrophils; studies aimed at defining the mechanisms of action of adenosine in this process have demonstrated that adenosine inhibits the translocation of the cytosolic enzyme 5‐lipoxygenase to nuclear structures, a process required for leukotriene biosynthesis in neutrophils. Our studies also demonstrated that exposure of human neutrophils to the adenosine A 2a receptor agonist CGS‐21680 result in a profound inhibition of the release of arachidonic acid upon cell stimulation. While the previously reported inhibitory effect of adenosine on calcium influx elicited in ligand‐activated neutrophils does not appear to be involved in the inhibitory effects of adenosine on leukotriene biosynthesis, strong evidence supports the implication of elevation of intracellular cyclic AMP concentration both in the inhibition of 5‐lipoxygenase translocation and arachidonic acid release. Drug Dev. Res. 52:397–405, 2001. © 2001 Wiley‐Liss, Inc.
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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 | 0.002 | 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) | 0.001 | 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 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".