PI3K accelerates, but is not required for, neutrophil chemotaxis to fMLP
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Bibliographic record
Abstract
PI3K activity, resulting in the accumulation of PIP(3) along the leading edge of a chemotaxing cell, has been proposed to be an indispensable signaling event that is required for cells to undergo chemotaxis to endogenous and exogenous chemoattractants. Some studies have suggested that this might be the case for chemoattractants such as IL8, whereas chemotaxis to other stimuli, such as the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP), might occur normally in the absence of PI3K activity. Herein, we systematically analyze the role of PI3K in mediating chemotaxis to fMLP, both in vitro and in vivo. Using short- and long-term in vitro assays, as well as an in vivo chemotaxis assay, we investigated the importance of PI3K in response to the prototypic chemoattractant fMLP. Exposure of neutrophils to fMLP induced an immediate polarization, which resulted in directional migration towards fMLP within 2-3 minutes. PI3K-inhibited cells also polarized and migrated in a directional fashion towards fMLP; however, this process was delayed by approximately 15 minutes, demonstrating that PI3K accelerates the initial response to fMLP, but an alternative pathway replaces PI3K over time. By contrast, p38-MAPK-inhibited cells, or cells lacking MK2, were unable to polarize in response to fMLP. Long-term chemotaxis assays using a pan-PI3K inhibitor, a PI3Kdelta-specific inhibitor or PI3Kgamma-knockout neutrophils, demonstrated no role for PI3K in mediating chemotaxis to fMLP, regardless of the steepness of the fMLP gradient. Similar results were observed in vivo, with PI3Kgamma(-/-) cells displaying a delayed, but otherwise normal, chemotactic response to gradients of fMLP. Together, these data demonstrate that, although PI3K can enhance early responses to the bacterial chemoattractant fMLP, it is not required for migration towards this chemoattractant.
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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) | 0.000 | 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 it