Neutrophil Infiltration of the Colon Is Independent of the FPR1 yet FPR1 Deficient Mice Show Differential Susceptibilities to Acute Versus Chronic Induced Colitis
Bibliographic record
Abstract
BACKGROUND: The receptor for formylated peptides, formyl peptide receptor 1 (FPR1), potently activates and serves as a chemoattractant receptor for neutrophils. AIM: Given the abundance of neutrophils in the inflamed colon, our aim was to determine if the FPR1 mediates colonic neutrophil migration, using the dextran sodium sulfate (DDS)-induced model of colitis. METHODS: Formyl peptide receptor 1 gene-deficient mice were administered DDS in drinking water for a single 5-day period (acute) or in two 5-day periods separated by 16 days (chronic). At the end of the treatment their colons were excised, measured, and prepared for histological evaluation. RESULTS: FPR1(-/-) mice experienced less severe acute colonic pathology than C57BL/6 (wildtype) mice. The opposite was observed following the second colitis cycle, with FPR1(-/-) mice developing worse pathology than wildtype mice. Both strains had similar numbers of infiltrating neutrophils in ulcerated areas of the colon after a single DSS cycle, but FPR1(-/-) mice had significantly more neutrophils in the ulcerated mucosa after two cycles. There was no difference in the capacity of neutrophils from each strain to migrate to chemoattractants. Since the FPR1(-/-) mice had larger ulcers compared to the wildtype mice, we propose that the FPR1(-/-) mice failed to recover at the same rate as wildtype mice. This apparent difference in restitution could not be attributed to observable differences in annexin A1. CONCLUSIONS: We conclude that neutrophil migration into the inflamed mouse colon does not depend on FPR1 but that FPR1 contributes in other pathological mechanisms that are harmful during acute inflammation but protective during chronic inflammation.
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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) | 0.000 | 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) | 0.000 | 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".