Endothelial Cell Calpain Activity Facilitates Lymphocyte Diapedesis
Bibliographic record
Abstract
Lymphocyte infiltration of tissue is a cardinal feature of solid-organ allograft rejection. Vascular endothelial cells (EC) participate in lymphocyte recruitment through the display of adhesion molecules and chemokines to promote leukocyte extravasation. Moreover, EC reorganize the cytoskeleton and cytoskeleton-associated structures during leukocyte diapedesis. We examined the role of EC (Ca+2)i and the calcium-sensitive protease, calpain, during lymphocyte diapedesis through a human EC monolayer under physiologic shear stress in vitro. We observed that lymphocyte transendothelial migration (TEM) was inhibited by chelating EC cytosolic calcium, or depleting EC endoplasmic reticulum calcium stores by inhibition of the endoplasmic reticulum Ca ATPase. Further, inhibition of EC phospholiase C also decreased lymphocyte TEM. We determined that EC constitutively exhibit calpain activity, using fluorescence generation from a calpain substrate to report calpain activity in individual live cells. Moreover, EC adjacent to a transmigrating lymphocyte showed increased calpain activity. Further, lymphocyte TEM was inhibited by agents that block calpain activity. Inhibition of lymphocyte TEM occurs at the lumenal EC surface and correlates with impaired development of intercellular adhesion molecule 1 (ICAM-1)-rich docking structures by the EC. We conclude EC calcium and calpain activity facilitates lymphocyte TEM, and participates in the assembly of the docking structure.
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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 | 0.001 |
| 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 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".