PB0415 The Role of Filamin a in Platelet Thromboxane A2 Secretion
Bibliographic record
Abstract
Background: Kappa-Carrageenan (CGN) is a natural sulfated polysaccharide extracted from red algae.CGN has been studied for its potential thrombotic effects, as it has been shown to induce tail thrombosis in laboratory animals when administered intraperitoneally.Previous research has suggested that CGN can trigger platelet aggregation, but the cell-surface receptors and downstream signaling pathways involved in this process have not been fully understood.Aims: The aim of this study was to investigate CGN-induced platelet activation and its relationship with CGN-induced tail thrombosis (CTT).Methods: CGN was obtained from Sigma-Aldrich (#22048) and was dissolved in normal saline at concentrations ranging from 25μg/ml to 1 mg/ml.Platelet aggregation was evaluated using light-transmission aggregometry, and the expression of platelet activation markers was analyzed by flow cytometry.The signaling pathways involved in platelet activation were determined using Src family kinase inhibitors, Syk inhibitors, and Gq inhibitors.Intracellular tyrosine phosphorylation (Syk, LAT, PLCγ2) was confirmed by Western blotting.Washed platelets from CLEC-2 knockout mice or wild-type platelets treated with GPVI blocking antibodies (JAQ-1) were used to identify the cell-surface receptor.The length of tail thrombosis in wild-type and CLEC-2 deficient mice was also compared in the CTT model.Results: Our findings showed that CGN triggered platelet aggregation in a concentration-dependent manner, and that activated integrin αIIbβ3 and Pselectin were expressed.Inhibitor assay and platelet phosphorylation patterns indicated that CGN-induced platelet aggregation is dependent on the ITAM-receptor-based pathway.CGN-induced platelet aggregation was completely abolished in platelets from CLEC-2 deficient mice, but not in GPVI deficient mice.In vivo, the extent of tail thrombosis and thrombocytopenia was significantly inhibited in CLEC-2 deficient mice compared to wild-types.Conclusion(s): Our study provides evidence that CGN causes murine platelet activation through the tyrosine kinase family dependent downstream of CLEC-2, and that platelet activation via CLEC-2 is a pathogenic mechanism in CTT.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".