Regulation and Functional Effects of Monocyte Migration across Human Brain-Derived Endothelial Cells
Bibliographic record
Abstract
We have used human brain-derived endothelial cells (HBECs) maintained under basal culture conditions in a Boyden chamber assay system as an in vitro model of migration of cells of systemic immune origin across the blood brain barrier (BBB) during the initiation of a CNS-directed inflammatory response. In this study we evaluated the molecular mechanisms that regulate passage of ex vivo peripheral blood-derived monocytes across this barrier and the effects of such migration on the properties of both the HBECs and the monocytes. Our results indicate that monocytes can migrate across HBECs in the absence of inflammatory conditions, at rates exceeding those of lymphocytes. Monocyte migration could be significantly inhibited by the addition of blocking antibodies to intercellular adhesion molecule (ICAM)-1, very late antigen (VLA)-4 integrin, and monocyte chemoattractant protein (CCL-2/MCP-1), or treatment with tissue inhibitor of metalloproteinase (TIMP-1). Following monocyte migration there was a significant increase in permeability of soluble molecules and an enhanced rate of T cell migration across HBECs. The enhanced permeability could be partially prevented with anti-TNF-alpha antibody. The migration process did not induce the upregulation of either co-stimulatory molecules or chemokine receptors on the monocytes. These studies emphasize the functional role of monocyte-endothelial interactions in permitting target access of a CNS-directed cell-mediated immune response.
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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 | 0.000 | 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) | 0.000 | 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".