Pretreatment of Human Polymorphonuclear Leukocytes (PMN) with a New Carbon Monoxide (CO)‐Releasing Molecule (CORM401) Inhibits PMN Migration across Vascular Endothelial Cells
Bibliographic record
Abstract
Background We have demonstrated that carbon monoxide (CO)‐releasing molecules (CORMs) reduce septic inflammation by interfering with PMN recruitment to the inflamed organs. In this study, we assessed the effects/mechanisms of a newly synthesized Mn 2+ ‐based water‐soluble CORM (CORM401) on PMN adhesion(A)/transendothelial migration(TM) in an experimental model of endotoxemia in vitro. Methods Human umbilical vein endothelial cells (HUVEC) grown on parallel flow channels were stimulated with LPS (1μg/ml; 6 hrs) and interacted with freshly isolated PMN (pretreated for 30 min with CORM401 or its inactive compound, iCORM401; 100μM) for 5 min in the presence of 1.0 dyn/cm 2 shear stress. Subsequently, HUVEC:PMN co‐cultures were additionally perfused for 20 min with medium containing CORM/iCORM401. Video and confocal microscopy were used to analyze PMN A/TM. Results Stimulation of HUVEC with LPS significantly increased PMN A (0.6+/‐0.1 vs 30.9+/‐7.6 cells/mm 2 ; p<0.05) and TM (0.0 vs 41.7+/‐6.8%; p<0.001). Pretreatment of PMN with CORM401 had no effect on PMN A, however significantly reduced PMN TM (41.7+/‐6.8% vs 15.2+/‐4.3; p<0.01). The above findings were confirmed employing confocal microscopy. Conclusion CORM401 interferes with PMN recruitment by specific suppression of PMN migratory potential. (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".