Neutrophils Induce Sequential Focal Changes in Endothelial Adherens Junction Components: Role of Elastase
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Bibliographic record
Abstract
OBJECTIVE: In vitro studies have indicated that polymorphonuclear leukocytes (PMNs) traverse endothelial cell monolayers via the paracellular pathway (i.e., through endothelial cell-cell junctions. Herein, we assessed whether the adherens junctions (AJs) are disrupted during PMN transendothelial cell migration. METHODS: Human umbilical vein endothelial cells (HUVECs) were grown to confluence on porous membranes and activated with interleukin-1beta, and PMN transendothelial migration was facilitated by formyl-methionyl-leucyl-phenylalanine. Using dual immunofluorescence staining and laser scanning confocal microscopy, we assessed the effects of PMN-endothelial cell adhesive interactions (i.e., adhesion to and emigration across monolayers) on the AJ components vascular endothelial (VE)-cadherin, beta-catenin, alpha-catenin, and gamma-catenin. RESULTS: In the AJ immediately adjacent to the adherent PMN, there was a loss of staining for some of the AJ components. AJ components further away from HUVEC-PMN adhesive interactions were unaffected. An iterative approach indicated that the four components were sequentially lost from the AJ. beta-catenin was lost first, followed by VE-cadherin, alpha-catenin, and, finally, gamma-catenin. In the absence of PMNs, the cross-linking of VE-cadherin, but not platelet endothelial cell adhesion molecule-1 or intercellular adhesion molecule-1, increased the cytoplasmic accumulation of beta-catenin. During PMN transendothelial migration, all of the junctional components under study were lost at the immediate site of monolayer penetration. Again, at regions removed from the actual site of PMN penetration of the monolayers, the AJ components were unaffected. PMN-induced disorganization of the AJs was partially prevented by an elastase inhibitor. CONCLUSIONS: These findings suggest that adherent PMNs induce a localized, sequential disassembly of AJs, which is partially mediated by PMN-derived elastase and involves the initial loss of an intracellular component of AJs (i.e., beta-catenin).
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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 it