Linkage to the actin cytoskeleton is critical for α4β1‐mediated leukocyte rolling and chemokine‐induced arrest, but not prolonged adhesion
Bibliographic record
Abstract
The avidity or strength of integrin‐mediated cell adhesion is attributed to affinity (strength of individual bonds) and valency (number of bonds formed). We investigated the role of the actin cytoskeleton in α4β1 integrin mediated adhesion to VCAM‐1 in assays that model distinct steps of leukocyte emigration. In U937 cells stably transfected with the formyl peptide receptor, α4β1 integrin affinity up‐regulation induced by GPCR signaling remained intact following disruption of the actin cytoskeleton by cytochalasin D (cytoD) or latrunculin B (latB) (2 µM, 30 min incubation). Parallel plate flow chamber adhesion assays revealed that U937 cells pretreated with cytoD or latB failed to roll on surfaces coated with VCAM‐1 and arrest on surfaces co‐coated with VCAM‐1 and SDF‐1α. High affinity α4β1 induced by Mn2+ independent of GPCR signaling mediated spontaneous U937 arrest, which was blocked by cytoD or latB pretreatment. In contrast, U937 cell adhesion in 15 min assays was not inhibited by cytoD or latB. Fluorescence recovery after photobleaching demonstrated increased diffusion of α4β1 integrins in cells pretreated with cytoD, consistent with a disruption of integrin linkage to the actin cytoskeleton. These studies suggest that constitutive linkage of α4β1 integrins to the actin cytoskeleton is critical for mediating α4β1‐dependent rolling and arrest, but not prolonged leukocyte adhesion. Funded by CIHR.
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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".