A distinct subcellular pool and an α <sub>1G</sub> T‐type Ca <sup>2+</sup> channel regulated surface expression of P‐selectin in pulmonary capillary endothelium
Bibliographic record
Abstract
Regulated P‐selectin surface expression provides a rapid measure of endothelial transition to a pro‐inflammatory phenotype. In general, P‐selectin surface expression results from Weibel‐Palade body (WPB) exocytosis. Yet, it is unclear whether pulmonary capillary endothelium possesses WPBs or regulated P‐selectin surface expression. We used immunohistochemistry, immunofluorescence, ultrastructural assessment, and an isolated perfused lung model to demonstrate that capillary endothelium lacks WPBs, but possesses P‐selectin. Thrombin stimulated P‐selectin surface expression in both extra‐alveolar vessel and capillary endothelium. Only in capillaries was the thrombin‐stimulated P‐selectin surface expression markedly reduced by pharmacological inhibition of T‐type Ca 2+ channels, or by genetically eliminating T‐type channel α 1G ‐subunits. T‐type channel‐mediated cytosolic Ca 2+ transients were detected by real‐time imaging of fura‐2‐loaded capillary endothelium following plasma membrane depolarization via high K + perfusion. Depolarization also induced P‐selectin surface expression in capillary endothelium, which was abolished by T‐type channel blockade or eliminating α 1G ‐subunits. Collectively, these findings indicate that, in capillary endothelium, subcellular P‐selectin is WPB‐independent, and its regulated surface expression is driven by mechanism(s) distinct from WPB exocytosis; namely, Ca 2+ entry through the α 1G T‐type channel controls the regulated P‐selectin surface expression in capillary endothelium.
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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) | 0.001 | 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".