Differential Regulation of Lung Endothelial Permeability <b><i>in Vitro</i></b> and <b><i>in Situ</i></b>
Bibliographic record
Abstract
In the lungs, increased vascular permeability can lead to acute lung injury. Because vascular permeability is regulated primarily by endothelial cells, many researchers have studied endothelial cell monolayers in culture, in order to understand the pathomechanisms of pulmonary edema. Such studies are based on the assumption that endothelial cells in culture behave like endothelial cells in situ. Here we show that this assumption is largely unfounded. Cultured endothelial cells show profound differences compared to their physiological counterparts, including a dysregulated calcium homeostasis. They fail to reproduce the pulmonary responses to agents such as platelet-activating factor. In contrast, they respond in a Rho-kinase depend fashion to thrombin, LPS or TNF. This is a striking finding for three reasons: (i) in the lungs, none of these agents increases vascular permeability by a direct interaction with endothelial cells; (ii) The endothelial Rho-kinase pathway seems to play little role in the development of pulmonary edema; (iii) This response pattern is similar for many endothelial cells in culture irrespective of their origin, which is in contrast to the stark heterogeneity of endothelial cells in situ. It appears that most endothelial in culture tend to develop a similar phenotyp that is not representative of any of the known endothelial cells of the lungs. We conclude that at present cultured endothelial cells are not useful to study the pathomechanisms of pulmonary edema.
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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 | 0.001 | 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".