Activation of SHIP by NADPH Oxidase-stimulated Lyn Leads to Enhanced Apoptosis in Neutrophils
Bibliographic record
Abstract
Neutrophils undergo rapid spontaneous apoptosis. Multiple antiapoptotic stimuli can inhibit this process via activation of the Akt pathway. However, despite no such effect singly, combined anti- and proapoptotic stimuli inhibit Akt activity, leaving the cells susceptible to accelerated apoptosis. The blockade of Akt activation depended on reduced phosphoinositide 3,4,5-trisphosphate levels but not decreased phosphatidylinositol 3-kinase activity, thus implicating the involvement of an inositol phosphatase. Evidence for SHIP involvement was provided by SHIP localization to membrane receptors and subsequent activation along with the observed inability of SHIP -/- neutrophils to exhibit enhanced apoptosis with the stimulus combination. Activation of SHIP was found to depend on Lyn activation, and this, in turn, required NADPH oxidase. Neutrophils from chronic granulomatous disease patients and Lyn -/- mice no longer responded to the combined stimuli. Thus, we propose a role for oxidants and Lyn in SHIP regulation and suggest a novel mechanism for regulating neutrophil apoptosis.
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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 | 0.000 | 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 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".