Fundamentally different roles for LFA-1, Mac-1 and α4-integrin in neutrophil chemotaxis
Bibliographic record
Abstract
Although the LFA-1, Mac-1 and alpha(4) integrins are required for chemotaxis, it is unknown how they are regulated or what specific role they play. Previously we demonstrated that fMLP and IL-8 induce chemotaxis via the p38 MAPK and phosphoinositide 3-kinase (PI3K) pathways, respectively. Here we show that these chemoattractants also activate and use Mac-1 and LFA-1 in a differential manner during chemotaxis. Using integrin-specific substrata, we demonstrate that cell movement in response to IL-8 is mediated by Mac-1, whereas LFA-1 is required for directional migration. By contrast, chemotaxis to fMLP requires Mac-1 for cell movement, whereas LFA-1 and alpha(4)-integrin are required for directional migration. On serum protein, which contains ligands for LFA-1, Mac-1 and alpha(4)-integrin, chemotaxis to fMLP is dependent on Mac-1, whereas chemotaxis to IL-8 is dependent on LFA-1. These results suggest that Mac-1 is the dominant integrin involved in chemotaxis to fMLP, and LFA-1 is the dominant integrin involved in chemotaxis to IL-8. Consistent with these observations, higher quantities of high-affinity Mac-1 are found on cells chemotaxing to fMLP then on cells chemotaxing to IL-8. Moreover, a much larger quantity of clustered LFA-1 was found on cells migrating to IL-8 compared to cells moving towards fMLP. When cells are presented with competing gradients of fMLP and IL-8, they preferentially migrate towards fMLP and activate/utilize integrins in a manner identical to fMLP alone. Under the same conditions, p38 MAPK inhibition abolishes the preferential migration to fMLP; instead, the cells migrate preferentially towards IL-8. The activation and utilization of integrins under these conditions are consistent with patterns observed with IL-8 alone. Together, these data suggest that fMLP and IL-8 differentially activate integrins for use during chemotaxis, that p38 MAPK is a major mediator in the activation and utilization of integrins, and selective integrin activation occurs during chemotaxis between opposing gradients.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 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".