Lipid efflux in human and mouse macrophagic cells: evidence for differential regulation of phospholipid and cholesterol efflux
Bibliographic record
Abstract
ABCA1 is a critical regulator of lipid efflux from cells, which is highly regulated at the transcriptional and posttranslational levels. However, cells from different species and different tissues, and primary versus immortalized cells, show different modes of regulation. We have carried out a comparative analysis of basic signaling pathways of lipid efflux in mouse J774 cells, mouse peritoneal macrophages (MPMs), human THP-1 cells, and human monocyte-derived macrophages. Cyclic AMP (cAMP) was a potent stimulator of lipid efflux in mouse macrophages, but not in human macrophages. Moreover, this cAMP-inducible component of efflux from MPMs was inhibitable by H89 [a protein kinase A (PKA) inhibitor], but H89 did not affect basal efflux. On the other hand, cAMP failed to show any stimulatory effect in human macrophages, but basal efflux was inhibitable by H89. In MPMs and THP-1 cells, protein kinase C (PKC) inhibitors blocked cholesterol efflux but had no effect on phospholipid efflux, demonstrating the separation of the regulation of phospholipid efflux and cholesterol efflux in macrophages. We conclude that: 1) cAMP regulates lipid efflux predominantly in a PKA-dependent fashion; 2) cholesterol efflux is modulated by a PKC-dependent mechanism; and 3) mouse and human macrophages exhibit different modes of regulation of lipid efflux.
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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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 | 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".