The role of 12-lipoxygenase in regulating megakaryocyte maturation and platelet-like particles production
Bibliographic record
Abstract
Megakaryocytes, a type of myeloid cell primarily produced in the bone marrow, are essential for releasing platelets into the bloodstream. Through platelet production, megakaryocytes transfer their own biological content to these cells, including inflammatory enzymes. Amongst these enzymes, 12-lipoxygenase (12-LO) has been shown to modulate platelet activation and is involved in several chronic inflammatory conditions. However, the role of 12-LO in megakaryocyte maturation and the subsequent release of platelets remains uninvestigated. This study demonstrates the importance of 12-LO expression in megakaryocyte maturation and functions. Flow cytometry and fluorescence microscopy were utilized to analyze DAMI cell differentiation. Inflammatory enzyme profiles were assessed through Western blot analysis and LC-MS/MS. To evaluate megakaryocyte functionality, platelet-type 12-LO knockout mice were employed. Differentiation of DAMI cells into mature megakaryocytes resulted in increased surface marker expression, enhanced platelet-like particle production, reduced cell proliferation, and elevated cell death. The arachidonic acid release from cell membranes was increased in differentiated cells as well as the expression of several inflammatory enzymes such as 12-LO, cyclooxygenase-1 and thromboxane synthase. The production of 12( S )-hydroxyeicosatetraenoic acid and thromboxane was also increased in these cells. In DAMI cells deficient in 12-LO expression (ALOX12 −/− ), we found no difference in CD41 expression following differentiation compared to ALOX12 +/+ cells. However, 12-LO-deficient cells produced fewer proplatelets and, consequently, fewer platelet-like particles. In vivo , platelet counts in 12-LO-deficient mice were comparable to those in wild-type mice, and the number of bone marrow megakaryocytes remained consistent between the groups. Ex vivo analysis revealed that megakaryocytes lacking 12-LO produced fewer platelets. These findings indicate that 12-LO may play a regulatory role in megakaryocyte function, particularly in proplatelet formation and platelet release.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".