Functional Platelet‐derived Mitochondria Induce the Release of Neutrophil Microparticles
Bibliographic record
Abstract
INTRODUCTION Inflammation is an essential process of the host defense against infections, illness, or tissue injuries. However, unregulated inflammation has been associated with chronic inflammatory auto‐immune diseases, such as rheumatoid arthritis, multiple sclerosis and atherosclerosis. Polymorphonuclear neutrophils (PMNL) are amongst the immune cells involved in the acute inflammatory response used to fight bacterial infections. Once activated, PMNL release inflammatory mediators, enzymes and large quantities of microparticles in the extracellular milieu to recruit various immune cells required to fight the invading pathogens. Recent evidence also shows that platelets (PLTs), well known for their coagulation proprieties, are also implicated in the body’s inflammatory response. Interestingly, activated PLTs can release fully functional mitochondria in the extracellular milieu. Known as the powerhouse of the cell, the mitochondria share similar characteristics with bacteria. Therefore, we hypothesize that PLTs‐derived mitochondria present in the extracellular milieu, acting in a similar way as bacteria, induce a sterile inflammatory response that involves the PMNL. OBJECTIVES The main objective of this study is to investigate the sterile inflammatory response of PMNL caused by the exposure of PLTs‐derived extracellular mitochondria. METHODS Blood was obtained from healthy consenting donors, then PMNL and PLTs‐derived mitochondria were isolated and purified. Following the co‐incubation of PMNL with various physiological doses of PLTs‐derived mitochondria, a characterization of the interaction between PMNL and PLTs‐derived mitochondria and an investigation of the inflammatory proprieties of PMNL was performed using flow cytometry, confocal microscopy, and high‐resolution respirometry. RESULTS Our data demonstrates that PLTs‐derived mitochondria associate with PMNL as quickly as 2 hours. This results in an increase of the PMNL intracellular calcium content and a 2.47‐fold mitochondrial‐dependent increase in oxygen consumption. Data also shows that PLTs‐derived mitochondria significantly induce, in a dose‐dependent manner, the release of PMNL microparticles. CONCLUSIONS This study provides a new insight into the role of PLTs‐derived mitochondria in the context of sterile inflammation. Specifically, the characterization of its interaction with PMNL reveals a novel modulator in the fundamental inflammatory response. The knowledge gained from this study provides insight into the mechanism of sterile inflammation in auto‐immune diseases. Support or Funding Information Canadian Institutes of Health Research, New Brunswick Health Research Foundation, New Brunswick Innovation Foundation
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".