Abstract 350: Interaction Of Methicillin-resistant Staphylococcus Aureus With Endothelial Cells Increase Intercellular Permeability By Activating Vasopressin Receptor-2.
Bibliographic record
Abstract
More than 700,000 people a year suffer from sepsis in the United States. From sheep studies, we reported that methicillin-resistant Staphylococcus aureus (MRSA) sepsis is associated with vascular hyperpermeability and that vasopressin receptor-2 (V2R) might be involved in this complication. Vascular hyperpermeability is associated with high mortality and new pharmacological targets are required to design new treatments. We hypothesized that in MRSA induced vascular hyperpermeability, peroxynitrite stimulates V2R to release potent angiogenic growth factor angiopoietin-2. Methods: Human lung microvascular endothelial cells (HMVECs) were incubated with MRSA plus peroxynitrite decomposition catalyst (FeTMPyP), angiopoietin-2 antibody or tie-2 antibody as well as with MRSA only. Permeability assay (FITC-Dextran quantification across the confluent cell monolayer) was then performed after the different treatments. To strengthen the hypothesis, HMVECs were then treated with MRSA, peroxynitrite or V2R selective agonist (desmopressin). Cell lysates from each treatment were screened for levels of V2R mRNA using RT-PCR. Results: 1) Permeability was significantly higher in cells treated with MRSA compared to control. 2) Permeability was significantly lower in cells treated with MRSA plus FeTMPyP, angiopoietin-2 antibody, and tie-2 antibody compared to cells treated with MRSA only. 3) Cells treated with MRSA, peroxynitrite and desmopressin had significant higher levels of V2R mRNA compared to control. Conclusion: When MRSA interacts with endothelial cells, intercellular permeability is increased suggesting disruption of tight junctions. Peroxynitrite is a player of this phenomenon by activating V2R. Angiopoietin-2 also has an important role disrupting intercellular junctions with tie-2 receptor as the mediator. Further studies have to be performed to know whether V2R activation release angiopoietin-2.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".