The Src Family Tyrosine Kinase fyn Protects Mice from Inflammation‐induced Lung Injury
Bibliographic record
Abstract
Endothelial cell apoptosis is an early event in the development of inflammatory lung diseases such as acute respiratory distress syndrome (ARDS) and bronchopulmonary dysplasia (BPD). In studies utilizing cultured human pulmonary endothelial cells we have shown that the Src family tyrosine kinase (STK) yes activated caspase‐3, while the STK fyn inhibited caspase‐3 activation. Therefore, in this study we tested the hypothesis that mice deficient in fyn will have more severe lipopolysaccharide (LPS)‐induced pulmonary apoptosis and lung injury than will similarly treated wild‐type mice. Wild‐type and fyn −/− mice (all on the same 129S1/SvImJ background) were given LPS 10 mg/kg intraperitoneally or saline for 24 hours and lungs were harvested for determination of proteins related to apoptosis. LPS treatment resulted in greater levels of cleaved caspase‐8, cleaved caspase‐9, cleaved caspase‐3, and p21 in the lungs from fyn −/− mice than in the lungs from wild‐type mice. In a second set of studies, lung sections from wild‐type and fyn −/− mice were stained for platelet endothelial cell adhesion molecule‐1 (PECAM‐1), we found that the fyn −/− mice had less PECAM‐1 expression, thicker alveolar septa, and more leukocyte infiltration than did wild‐type mice. In another set of studies wild‐type and fyn −/− mice were given LPS 2 mg/kg intratracheally or an equal volume of saline, and 24 hours later lung mechanics were measured using a Flexivent system (SCIREQ, Montreal, Canada). The fyn −/− mice had significantly (p<0.01) lower lung compliance (0.030 ± 0.003 ml/cmH 2 O) than did wild‐type mice (0.040 ± 0.001 ml/cmH 2 O). The fyn −/− mice also had significantly (p<0.05) higher tissue elastance (32.6 ± 3.1 cmH 2 O/mL) than did wild‐type mice (23.8 ± 0.8 cmH 2 O/mL). The fyn −/− mice had greater (p = 0.046) lung resistance (0.67±0.06 cmH 2 O/ml/s) than did wild‐type mice (0.55±0.02 cmH 2 O/ml/s). These results demonstrate that mice lacking fyn develop more apoptosis and more severe lung injury following LPS exposure than do wild‐type mice. These findings demonstrate that fyn is an important negative regulator of LPS‐induced apoptosis and the resultant lung injury in a mouse model of inflammatory lung diseases such as ARDS.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".