Serum amyloid A (SAA) prevents mitochondrial dysfunction and delays constitutive neutrophil apoptosis
Bibliographic record
Abstract
Elevated plasma levels other acute‐phase protein SAA have been used as a marker of inflammatory diseases. We investigated whether SAA could modulate constitutive neutrophil apoptosis that is critical to the optimal expression and resolution of inflammation. Culture of human neutrophils with SAA (0.1–20 ìg/ml) markedly prolonged neutrophil longevity by delaying spontaneous apoptosis (assessed by annexin V binding and nuclear DNA content) within 24–48 h of culture. The formyl peptide receptor antagonist N‐t‐Boc‐Phe‐Leu‐Phe‐Leu‐Phe that blocks binding of SAA to its receptor (termed FPRL‐1 or ALX) almost completely abrogated the SAA effects. SAA evoked concurrent activation of the extracellular signal‐regulated kinase (ERK) and phosphatidylinositol 3‐kinase/Akt, leading to phosphorylation of BAD at Ser112 and Ser136, respectively. These led to prevention of collapse of mitochondrial transmembrane potential and mitochondrial cytochrome c release, resulting in decreased caspase‐3 activity. Consistently, pharmacological inhibition of either ERK or phosphatidylinositol 3‐kinase partially prevented these actions of SAA. Co‐treatment of neutrophils with SAA and the pan‐caspase inhibitor Z‐VAD‐FMK (20 μM) resulted in similar suppression of apoptosis than SAA or Z‐VAD‐FMK alone. Our results indicate that SAA at clinically relevant concentrations promotes neutrophil survival by suppressing the constitutively expressed apoptotic machinery, and thus may contribute to prolongation and/or amplification of the inflammatory response. (Supported by CIHR grant MOP‐64283).
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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) | 0.001 | 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".