The path of murine serum amyloid a through peritoneal macrophages
Bibliographic record
Abstract
Serum amyloid A (SAA) is a family of proteins encoded by four related genes. Of the four, isoforms 1.1 and 2.1 are acute phase proteins synthesized by the liver. They become major components of the HDL plasma fraction during acute tissue injury and the HDL/SAA complex is readily taken up by macrophages. Herein we investigated the path SAA follows when presented to macrophages as HDL/SAA or in liposomes. Using antibodies specific to SAA and confocal microscopy, or EM autoradiography where only SAA is radio-labeled, we show that HDL/SAA is taken up rapidly by macrophages and within 30 min SAA, or fragments thereof, proceeds through the cytoplasm to the peri-nuclear region and then the nucleus. Within 45-60 min SAA, or fragments thereof, is found back in the cytoplasm and at the plasma membrane where it is subsequently extruded. The observation that SAA, or fragments thereof, traverse the nucleus is a novel finding and may implicate SAA in macrophage gene regulation. It also raises questions by what mechanism SAA enters and leaves the nucleus. We further investigated if both SAA isoforms traffic through the macrophage in a similar manner. Isoform differences were observed. Both isoforms bind well to the plasma membrane of macrophages at 4 degrees C, but at 37 degrees C only SAA2.1 is taken up by the cell in significant quantity, and is observed in the nucleus, suggesting that the two isoforms are handled differently and that they may have discrete physiological roles.
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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".