High circulating angiopoietin-2 levels exacerbate pulmonary inflammation but not vascular leak or mortality in endotoxin-induced lung injury in mice
Bibliographic record
Abstract
Background Elevated plasma levels of angiopoietin-2 (ANGPT2) have been reported in patients with acute lung injury (ALI); however, it remains unclear whether this increase contributes to, or just marks, the underlying vasculopathic inflammation and leak associated with ALI. Here we investigated the biological consequences of inducing high circulating levels of ANGPT2 in a mouse model of endotoxin-induced ALI. Methods Transgenic mice (ANGPT2 OVR ) with elevated circulating levels of ANGPT2, achieved through conditional hepatocyte-specific overexpression, were examined from 3 to 72 hours following lipopolysaccharide (LPS)-induced ALI. An aptamer-based inhibitor was used to neutralise the effects of circulating ANGPT2 in LPS-exposed ANGPT2 OVR mice. Results Total cells, neutrophils and macrophages, as well as inflammatory cytokines, were significantly higher in bronchoalveolar lavage (BAL) of ANGPT2 OVR versus littermate control tTA mice at 48 hours and 6 hours post-LPS, respectively. In contrast, LPS-induced vascular leak, evidenced by total BAL protein levels and lung wet/dry ratio, was unchanged between ANGPT2 OVR and controls tTA , while BAL levels of IgM and albumin were decreased in ANGPT2 OVR mice between 24 hours and 48 hours suggesting a partial attenuation of vascular leak. There was no significant difference in LPS-induced mortality between ANGPT2 OVR and controls tTA . An ANGPT2-neutralising aptamer partially attenuated alveolar cell infiltration while exacerbating vascular leak in LPS-exposed ANGPT2 OVR mice, supported by underlying time-dependent changes in the lung transcriptional profiles of multiple genes linked to neutrophil recruitment/adhesion and endothelial integrity. Conclusions Our findings suggest that high circulating ANGPT2 potentiates endotoxin-induced lung inflammation but may also exert other pleiotropic effects to help fine-tune the vascular response to lung injury.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".