PrP is cleaved from the surface of mast cells by ADAM10 and proteases released during degranulation
Bibliographic record
Abstract
While several functions of the endogenous prion protein have been studied, the homeostatic function of prion protein is still debated. Notably, prion protein is highly expressed on mast cells, granular immune cells that regulate inflammation. When activated, mast cells shed prion protein, although the mechanism and consequences of this are not yet understood. First, we tested several mast cell lines and found that, while prion protein was almost always present, the total amount differed greatly. Activation of mast cells induced a cleavage of the N-terminal region of prion protein, and this was reduced by protease inhibitors. Exogenous mast cell proteases caused a similar loss of the prion protein N-terminus. Additionally, mast cells shed prion protein in an ADAM10-dependent fashion, even in the absence of activation. Our results suggest that prion protein is cleaved from resting mast cells by ADAM10 and from activated mast cells by mast cell proteases. Prion protein also appears to affect mast cell function, as Prnp-/- bone marrow-derived mast cells showed lower levels of degranulation and cytokine release, as well as lower levels of both FcεRI and CD117. Finally, we sought to provide clinical relevance by measuring the levels of prion protein in bodily fluids of asthmatic patients, a disease that involves the activation of mast cells. We found an N-terminal fragment of prion protein could be detected in human sputum and serum, and the amount of this prion protein fragment was decreased in the serum of patients with asthma.
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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 | 0.001 |
| 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) | 0.001 | 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".