Hypertonic inhibition of exocytosis in neutrophils: central role for osmotic actin skeleton remodeling
Bibliographic record
Abstract
Hypertonicity suppresses neutrophil functions by unknown mechanisms. We investigated whether osmotically induced cytoskeletal changes might be related to the hypertonic inhibition of exocytosis. Hyperosmolarity abrogated the mobilization of all four granule types induced by diverse stimuli, suggesting that it blocks the process of exocytosis itself rather than individual signaling pathways. Concomitantly, osmotic stress provoked a twofold increase in F-actin, induced the formation of a submembranous F-actin ring, and abolished depolymerization that normally follows agonist-induced actin assembly. Several observations suggest a causal relationship between actin polymerization and inhibition of exocytosis: 1) prestimulus actin levels were inversely proportional to the stimulus-induced degranulation, 2) latrunculin B (LB) prevented the osmotic actin response and restored exocytosis, and 3) actin polymerization induced by jasplakinolide inhibited exocytosis under isotonic conditions. The shrinkage-induced tyrosine phosphorylation and the activation of the Na(+)/H(+) exchanger were not affected by LB. Inhibition of osmosensitive kinases failed to prevent the F-actin change, suggesting that the osmotic tyrosine phosphorylation and actin polymerization are independent phenomena. Thus cytoskeletal remodeling appears to be a key component in the neutrophil-suppressive, anti-inflammatory effects of hypertonicity.
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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) | 0.001 | 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 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".