E/P-selectin-deficient mice: an optimal mutation for abrogating antigen but not tumor necrosis factor-α-induced immune responses
Bibliographic record
Abstract
Leukocyte recruitment in cremaster microcirculation was visualized by intravital microscopy, either in ovalbumin sensitized and challenged animals, or in response to TNF-alpha. In antigen-challenged mice a significant increase in leukocyte rolling (approximately 50 to 200-300 cells/min) and adhesion (2 to 15-20 cells/100 microm), and a very dramatic increase in emigration ( approximately 1 to >40 cells/field) was observed over 24 h. Although rolling and adhesion was dramatically blunted in P-selectin- or P selectin/ICAM-1-deficient mice, emigrated cell number was similar to that observed in wild-type mice. Leukocyte rolling, adhesion and emigration was almost entirely abrogated over 24 h in E/P-selectin-deficient mice, demonstrating that antigen-induced leukocyte recruitment can be entirely disrupted in the absence of both endothelial selectins. However, E/P-selectin-deficient mice were able to recruit leukocytes at 24 h after TNF-alpha challenge. Rolling 24 h post-TNF-alpha in E/P-selectin-deficient mice was not inhibitable with anti-L-selectin antibody, suggesting an entirely selectin-independent pathway of rolling. We identified this pathway to be alpha (4)-integrin dependent and demonstrated that VCAM-1 expression was increased only in mice challenged with TNF-alpha. These data demonstrate that, in vivo, sufficient amounts of TNF-alpha can recruit leukocytes independently of selectins, whereas inhibition of endothelial selectins is the optimal intervention in reducing the immune response to antigen.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 teacher head, 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".