ICAM-1-mediated leukocyte adhesion is critical for the activation of endothelial LSP1
Bibliographic record
Abstract
Leukocyte-endothelial interaction triggers signaling events in endothelial cells prior to transendothelial migration of leukocytes. Leukocyte-specific protein 1 (LSP1), expressed in endothelial cells, plays a pivotal role in regulating subsequent recruitment steps following leukocyte adhesion. In neutrophils, LSP1 is activated by phosphorylation of its serine residues by molecules downstream of p38 MAPK and PKC. Whether leukocyte adhesion to endothelial cells is required for endothelial LSP1 activation remains elusive. In addition, discrepancies in the functions of endothelial and leukocyte LSP1 in leukocyte adhesion prevail. We demonstrate that adhesion of wild-type (Lsp1(+/+)) neutrophils to LSP1-deficient (Lsp1(-/-)) endothelial cells was significantly reduced compared with adhesion to Lsp1(+/+) endothelial cells. Immunoblotting revealed increased phosphorylated endothelial LSP1 in the presence of adherent Lsp1(-/-) neutrophils [stimulated by macrophage inflammatory protein-2 (CXCL2), TNF-α, or thapsigargin], but not cytokine or chemokine alone. Pharmacological inhibition of p38 MAPK by SB-203580 (10 μM) significantly blunted the phosphorylation of endothelial LSP1. Functionally blocking endothelial ICAM-1 or neutrophil β2-integrins diminished neutrophil adhesion and phosphorylation of endothelial LSP1. The engagement of endothelial ICAM-1 cross-linking, which mimics leukocyte adhesion, resulted in phosphorylation of endothelial LSP1. In neutrophil-depleted Lsp1(+/+) mice, administration of ICAM-1 cross-linking antibody resulted in increased phosphorylation of LSP1 and p38 MAPK in TNF-α-stimulated cremaster muscle. In conclusion, endothelial LSP1 participates in leukocyte adhesion in vitro, and leukocyte adhesion through ICAM-1 fosters the activation of endothelial LSP1, an effect at least partially mediated by the activation of p38 MAPK. Endothelial LSP1, in contrast to neutrophil LSP1, is not phosphorylated by cytokine or chemokine stimulation alone.
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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 | 0.001 |
| 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 | 0.002 |
| 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".