Molecular mechanisms of tumor necrosis factor α-stimulated leukocyte recruitment into the murine hepatic circulation
Bibliographic record
Abstract
To date, much of the adhesion work in the liver has been restricted to sinusoids and postsinusoidal venules. However, selectins have been localized on the portal (presinusoidal) venules and these vessels have been shown to be important in metastasis of tumors. The purpose of this study was to characterize the leukocyte-endothelial interactions within the 3 compartments of the hepatic microvasculature under baseline conditions and in response to tumor necrosis factor alpha (TNF-alpha). Mice deficient in P-selectin or both E- and P-selectin were compared with wild-type (C57Bl/6, wild type) mice. Animals were injected with murine TNF-alpha (15 microg/kg intraperitoneally [IP]) and the liver was examined by fluorescence intravital microscopy 4 hours later. Under baseline conditions, leukocyte flux in the portal venules was 1.42 +/- 0.42 cells/min. Leukocyte flux in the portal venules of wild-type mice increased 8-fold in response to 4 hours of TNF-alpha stimulation. This was reduced by 50% in the P-selectin-deficient mice but was not reduced further by either the addition of an E-selectin antibody (9A9, 100 microg intravenously [IV]) to these mice or in mice deficient in both E- and P-selectin. In P-selectin-deficient mice, the addition of an antibody against alpha(4)-integrin (R1-2, 75 microg IP) reduced rolling to baseline. But in the E- and P-double-selectin-deficient mice the addition of an antibody against L-selectin (Mel 14, 3 microg/kg IV) had no effect on TNF-alpha-induced recruitment. Similar responses were seen in the central venules, however, in the sinusoids the increased number of stationary leukocytes seen in response to 4 hours of TNF-alpha stimulation in the wild-type mice was not reduced in P-selectin-deficient mice with or without the alpha(4)-integrin antibody. These data suggest that leukocytes can use alpha(4)-integrin independent of the selectins in the venules. Within the sinusoids, however, inhibition of E-selectin, P-selectin, and alpha(4)-integrin was insufficient to reduce leukocyte recruitment.
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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 | 0.000 |
| 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".