Aspirin-triggered lipoxin enhances macrophage phagocytosis of bacteria while inhibiting inflammatory cytokine production
Bibliographic record
Abstract
The macrophage plays a major role in the induction and resolution phases of inflammation; however, how lipid mediator-derived signals may modulate macrophage function in the resolution of inflammation driven by microbes (e.g., in inflammatory bowel disease) is not well understood. We examined the effects of aspirin-triggered lipoxin (ATL), a stable analog of lipoxin A(4), on the antimicrobial responses of human peripheral blood mononuclear cell-derived macrophages and the monocytic THP-1 cell line. Additionally, we assessed the expression and localization of the lipoxin receptor, formyl peptide receptor 2 (FPR2), in colonic mucosal biopsies from patients with Crohn's disease to determine whether the capacity for lipoxin signaling is altered in inflammatory bowel disease. We found that THP-1 cells treated with ATL (100 nM) displayed increased phagocytosis of inert fluorescent beads and Escherichia coli in a scavenger receptor- and PI3K-dependent, opsonization-independent manner. This ATL-induced increase in phagocytosis was also observed in primary human macrophages, where it was associated with an inhibition of E. coli-induced IL-1β and IL-8 production. Finally, we found that FPR2 gene expression was increased approximately sixfold in the colon of patients with Crohn's disease, a finding reproduced in vitro by the treatment of THP-1 cells with interferon-γ or lipopolysaccharide. These results suggest that lipoxin signaling is upregulated in inflammatory environments, and, in addition to their known role in tissue resolution following injury, lipoxins can enhance macrophage clearance of invading microbes.
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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 | 0.000 |
| 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) | 0.000 | 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".