Extracellular mitochondria Released from Hepatic Ischemia Reperfusion Induce Macrophage activation both <i>in vitro</i> and <i>in vivo</i>
Bibliographic record
Abstract
Abstract Background During liver transplantation ischemia and reperfusion injury (IRI), an immune driven inflammatory response provoked by cellular oxygen deprivation, is unavoidable. The inflammatory responses, resulting from acute oxidative stress and consequent hepatocellular death during the early reperfusion phase, cause the release of endogenous danger signals. Recent studies show that the release of free mitochondria (FM) from deceased organ donors is directly linked with functionally important immune activation and early allograft dysfunction (Pollara, et al., 2018). Organs from donors after cardiocirculatory death (DCD) undergo a prolonged warm ischemia process compared with organs from donors after neurological determination of death (NDD), and therefore have more severe IRI. Herein, we investigated the roles of FM in liver IRI, particularly as related to macrophages. Methods Liver biopsies were assayed by TEM to assess for FM release. FM were co-cultured with macrophages (cell line, bone marrow derived macrophages, and primary Kupffer cells), and injected i.p. in vivo to explore the recruitment and activation of macrophages. Inflammatory mediators were tested by luminex. Results FM levels were significantly higher in IRI. Co-culture of FM with macrophages significantly increased inflammatory mediator release but this process was not Formyl Peptide Receptor 1 dependent. The injection of FM induced significant accumulation of monocyte-derived macrophages and activation of macrophages in the peritoneum. Conclusion Our results indicate that IRI can elicit significantly increased FM, and that FM from hepatic IRI can attract and activate macrophages, which may influence the outcome of liver transplantation.
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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 | 0.001 |
| 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".