Human diamine oxidase undergoes transcytosis and colocalizes with the plasma membrane monoamine transporter indicating intracellular histamine degradation
Bibliographic record
Abstract
Secreted human diamine oxidase (hDAO) is the only enzyme capable of extracellular histamine inactivation. Histamine is the key mediator released at high concentrations from activated mast cells causing various unpleasant to life-threatening symptoms. Recombinant hDAO is internalized into various cell types. However, rhDAO-containing intracellular vesicles do not colocalize with the lysosomes indicating that rhDAO is unlikely targeted for direct degradation. After internalization rhDAO was rapidly exocytosed without loss of enzymatic activity and re-internalized. Total internal reflection fluorescence microscopy revealed that rhDAO undergoes transcytosis in endothelial cells. The number of transcytosis events was dose-dependent and saturable indicating a specific, receptor-mediated uptake mechanism. Addition of unlabeled DAO, heparin and heparin-binding motif mutated DAO significantly reduced the number of transcytosis events. After intravenous injection of rhDAO into mice it was detected in vesicles not only within but also below the endothelial cell layer of the thoracic aorta. Localization of hDAO within extracellular vesicles was not detected in biological fluids. In various cell types intracellular vesicular rhDAO colocalized with plasma membrane monoamine transporter (PMAT), but not with the organic cationic transporters 1-3. Histamine is described to be a substrate for all four transporters. Cytoplasmic intravesicular localization of DAO has been detected for many decades but no definite physiological function could be assigned. Newly discovered transcytosis might transport DAO into the interstitial fluid compartment with widespread tissue distribution, especially during pregnancy. Vesicular colocalization of DAO with the histamine transporter PMAT indicates intracellular histamine degradation within these poorly characterized vesicles.
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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".