Alveolar macrophages (AM) from septic mice promote PMN transendothelial migration: an event involving c‐Src kinase‐mediated activation of NADPH oxidase within pulmonary endothelial cells (PEC)
Bibliographic record
Abstract
Sepsis is associated with an inflammatory response in the lungs. We have previously shown that AM obtained from septic mice can promote PMN migration across PEC monolayers. PEC NADPH oxidase activity was a prerequisite for the AM‐induced PMN migration. The upstream signaling pathways involved in the activation of PEC NADPH oxidase by septic AM are not clear. The purpose of the present study was to assess the role of tyrosine kinase c‐Src (c‐Src), phosphatidylinositol 3 kinase (PI‐3K), and MAPkinase (MAPK) in the activation of NADPH oxidase. Feces‐induced peritonitis (FIP) was used as a murine model of sepsis. AM isolated from mice 6 hrs after FIP or their supernatants (1 hr incubation of AM in MEM) were used in experiments. Supernatants from septic AM increased phosphorylation (activation) of PEC c‐Src kinase within 2min of exposure (as a point of reference NADPH oxidase activation in this system requires 5 min). Pretreatment of PEC with an inhibitor of c‐Src (PP2) prevented the 1) activation of the NADPH oxidase (lucigenin‐enhanced chemiluminescence) and 2) PMN transendothelial migration (cell culture inserts) induced by septic AM. Inhibitors of Erk1/2 (U0126), JNK (SP600125), or PI‐3 K (LY294002) did not prevent the activation of PEC NADPH oxidase by septic AM. Taken together, these findings indicate that c‐Src kinase (but not Erk1/2, JNK, or PI‐3K) is involved in the upstream signaling pathway (s) leading to activation of PEC NADPH oxidase by septic AM. Supported by CIHR (MGC‐12816)
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".