Syk mediates airway contractility independently of leukocyte function
Bibliographic record
Abstract
BACKGROUND: Syk plays a role in inflammatory diseases such as asthma and rheumatoid arthritis. We reported a role for epithelial expression of Syk in the airways hyperresponsiveness in a mouse model of asthma. These observations led us to posit a role of epithelial Syk in airway contractility. OBJECTIVE: To investigate the role of Syk in airway contractility in response to methacholine (MCh). METHODS: We used Syk flox/flox //rosa26CreER T2 conditional Syk knockout mice to evaluate respiratory mechanics and MCh-responsiveness in vivo using the ventilator-based flexiVent® system, and used live microscopy to assess airway contractility by measuring airway lumen diameter in lung slices ex vivo . RESULTS: In vivo studies showed that Syk-deficient mice were less responsive to MCh compared with Syk-intact mice. Central airways resistance (R N ) was significantly different between the Syk-intact and Syk-deficient mice (R N (max) : 2.06±0.29 vs 1.29±0.10, respectively, p < 0.05, n=6 and 8/group). The total and differential cell counts in the bronchoalveolar lavage fluid were similar between the two groups. In ex vivo lung slices, which are devoid of circulating leukocytes, MCh (100 mg/ml) induced a 20% reduction in the luminal area in the Syk-expressing mice to 80.5±0.6% of baseline. In contrast, MCh-induced contraction of the airways was virtually abrogated in ex vivo lung slices obtained from Syk-deficient mice (luminal area 92.2±0.6 % of baseline in Syk-deficient mice, n=4/group, p <0.05). CONCLUSIONS: These observations suggest that Syk mediates AHR independent of its role and function in leukocytes, and supports a potential paracrine role for airway epithelial Syk in modulating airway smooth muscle activity.
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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) | 0.001 | 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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".