Alveolar macrophage induced septic pulmonary microvascular endothelial cell injury is inducible nitric oxide synthase‐dependent
Bibliographic record
Abstract
We previously found that alveolar macrophage (AM) inducible nitric oxide synthase (iNOS) appeared essential for pulmonary microvascular protein leak in septic mice. However, the direct role of AM iNOS in septic lung injury or endothelial injury has not been addressed. Thus, we assessed the effects of AM iNOS on pulmonary microvascular endothelial cell (PMVEC) injury under septic conditions in vitro AM‐PMVEC co‐culture. Murine PMVEC were utilized as protein leak and neutrophil migration predominantly occur in the pulmonary microvasculature during septic lung injury. PMVEC were isolated and seeded on Transwell inserts (3.0ìm pore) and allowed to grow to confluence. In AM‐PMVEC co‐cultures stimulated with 3ng/ml cytomix (equal concentrations of TNF‐á, IL‐â and IFN‐ã) for 9 hours, the permeability of the PMVEC monolayer was assessed by the degree of Evans blue labeled albumin leak across the monolayer in the final hour of stimulation. The presence of wildtype (iNOS+/+) AM in the upper compartment dose‐dependently (1:1 and 3:1) increased trans‐PMVEC albumin leak (80.7 ± 18% of control in 1:1 vs. 265.1 ± 28% of control in 3:1). In contrast, presence of AM in the lower compartment had no effect on cytomix‐stimulated PMVEC albumin leak (128 ± 30% of control). When compared to co‐culture of PMVEC with iNOS+/+ AM, presence of iNOS knockout (−/−) AM, in a 3:1 ratio of AM to PMVEC, had no effect on cytomix‐stimulated trans‐PMVEC albumin leak. These data are consistent with a direct role of AM iNOS in the septic injury of PMVEC. This suggests an important role for AM iNOS in septic lung injury, and a possible new therapeutic approach.
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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".