GM-CSF-treated bone marrow-derived macrophages improve pulmonary fibrosis in bleomycin-treated mice
Bibliographic record
Abstract
Rationale: Pulmonary fibrosis (PF) is associated with collagen deposition, reduced pulmonary compliance, and mortality. In health, lung homeostasis is maintained by alveolar macrophages (AMs), which are functionally dependent on granulocyte macrophage-colony stimulating factor (GM-CSF). GM-CSF induces the expression of milk fat globulin E8 (MFGE8) in macrophages, which facilitates the clearance of apoptotic cells and collagen, thereby maintaining homeostasis. We have shown that, in the bleomycin (BLM) minipump model of PF, AM function impairment precedes the development of fibrosis, which coincides with a reduction in lung GM-CSF. We hypothesized that administration of GM-CSF-treated macrophages to BLM mice would improve pulmonary fibrosis. Methods: GM-CSF-treated bone marrow-derived macrophages (G-BMDMs) or PBS were administered oropharyngeally to PBS or BLM-treated mice 7 days after BLM initiation. At day 28, mice underwent pulmonary function testing. Histological assessment of apoptosis by TUNEL assay and lung collagen deposition by picrosirius red was performed. Lungs were snap frozen for hydroxyproline quantification and qRT-PCR of Mfge8. Results: Following BLM treatment, pulmonary compliance was impaired (p<0.0001) and collagen (p<0.0001), apoptotic cells (p=0.004), and hydroxyproline content (p=0.005) were elevated. Administration of G-BMDMs improved lung compliance (p=0.039), hydroxyproline content (p=0.014), collagen (p<0.0001), and number of apoptotic cells (p=0.004), and increased MFGE8 expression (p=0.007). Conclusion: The administration of G-BMDM to BLM mice significantly improved pulmonary fibrosis. Further investigations are merited to elucidate the role of MFGE8.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".