L-selectin stimulation enhances functional expression of surface CXCR4 in lymphocytes: implications for cellular activation during adhesion and migration
Bibliographic record
Abstract
L-selectin mediates leukocyte tethering and rolling, the first step in a sequential process of leukocyte adhesion and migration. Additionally, L-selectin has important signaling roles perhaps contributing to leukocyte activation and integrin-mediated adhesion. Because chemokines are critically involved in leukocyte activation, we questioned whether L-selectin signaling affects chemokine receptor expression and function. We observed that whereas only 5% to 15% of freshly isolated lymphocytes expressed CXCR4 on the cell surface, intracellular CXCR4 was detectable in all cells. Engagement of L-selectin by antibody cross-linking or the L-selectin ligands fucoidan or sulfatide mobilized intracellular CXCR4 to significantly increase surface CXCR4 expression but did not affect CCR5, CCR7, or beta2-integrin expression. L-selectin stimulation also inhibited stromal-derived factor 1 (SDF-1)-induced CXCR4 internalization. The combined effects of L-selectin on CXCR4 trafficking are likely important in markedly enhancing cell activation by SDF-1. Blockade of SDF-1-induced CXCR4 internalization resulted in enhanced actin polymerization on subsequent exposure to SDF-1. Physiologically more important, L-selectin stimulation increased SDF-1-induced lymphocyte adhesion and transendothelial migration, which were inhibited by anti-leukocyte function-associated antigen 1 antibodies, tyrosine kinase inhibitors, and pertussis toxin. To further corroborate the additive stimulating effects, L-selectin signaling and SDF-1 increased beta2-integrin activation. Taken together, L-selectin-mediated signals specifically enhance CXCR4 expression and function, suggesting a novel mechanism for the modulation of lymphocyte activation during cell adhesion and transmigration.
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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) | 0.002 | 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".