A new carbon monoxide (CO)‐releasing molecule (CORM401) suppresses PMN migratory potential through an F‐actin‐dependent mechanism
Bibliographic record
Abstract
Background Our previous work suggested that a newly synthesized Mn 2+ ‐based water‐soluble carbon monoxide (CO)‐releasing molecules (CORM401) interfered with PMN recruitment by inhibiting transendothelial migration across the endothelium. In this study, we further investigated the effects of CORM401 on PMN chemotaxis by an F‐actin‐dependent mechanism. Methods Freshly isolated human PMN were placed into a μ‐Slide chemotaxis chamber and allowed to migrate in response to an fMLP (10μM) gradient for 50 min in the absence or presence of 100 μM CORM401 or inactive CORM401(iCORM401). PMN migration was recorded and analyzed for migration directionality and velocity. To assess the effect of CORM401 on fMLP‐stimulated PMN function, F‐actin polymerization was measured by flow cytometry. In addition, the phosphorylation of MAPK and p21‐activated kinases (PAK) in PMN were examined by immunoblotting. Results Pre‐treating PMN with CORM401 significantly reduced their directionality and mean velocity (p<0.01) in response to fMLP compared to controls. CORM401 significantly reduced F‐actin polymerization in fMLP‐stimulated PMN (p<0.01). Pre‐treating PMN with CORM401 did not result in decreased MAPK phosphorylation, but resulted in decreased PAK phosphorylation (p<0.05). Conclusion CORM401 suppresses neutrophil migratory potential through an F‐actin‐dependent mechanisms. This study showed for the first time that the use of CORM401 has an effect on F‐actin‐dependent mechanisms of PMN. Support or Funding Information HSFO 393, IRF‐25‐12
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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 | 0.000 |
| 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 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".