Abstract 658: Macrophage Dynamics in Inflammation: Tree Ring--Like Growth of Macrophages in Layers Within Atherosclerotic Plaques
Bibliographic record
Abstract
The mechanisms that control macrophage accumulation and retraction from plaques are fervently debated. We had earlier wondered if monocyte-derived cells might be driven to become motile cells resembling dendritic cells, capable of leaving plaque, under conditions when macrophage content in plaques waned. Thus, our laboratory developed a technique that allows the use of fluorescent phagocytic tracers to quantitatively monitor macrophage influx into plaques as well as the potential emigration of macrophages out of plaques. The phagocytic tracer was not removed from plaques when plaque macrophage content receded in conjunction with a stark lowering of plasma cholesterol, arguing that macrophage loss does not result from robust emigration of macrophages out of plaques. Nonetheless, here we show that the distribution of the phagocytic tracer was very different under conditions when macrophage content wanes, as the tracer is distributed near the arterial lumen in this case, versus conditions when macrophages increase, when the tracer is located deep within plaques. Under all conditions and time points, the tracer remained equidistant from the internal elastic lamina that defined the border of the inflammatory plaque, indicating that tracer-bearing macrophages underwent no net displacement. Indeed, we could generate a tree-ring like appearance in plaques by labeling a second wave of monocytes with fluorescent particles of a different color than the first and show that they created a second layer, resembling growth of rings on an aging tree. Preliminary data from multiphoton imaging in atherosclerotic plaques supports the concept of restricted territories for plaque macrophages following recruitment. Under conditions when monocyte recruitment continues, previously recruited macrophages that get buried would likely be subjected to increasing hypoxia and related signals that are pro-inflammatory. This layering of macrophages on macrophages may itself drive a vicious cycle that perpetuates inflammation beyond through signals other than the signal that initiated plaque development in the first place.
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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) | 0.000 | 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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".