Inhibition of K+ efflux prevents mitochondrial dysfunction and suppresses constitutive apoptosis in human neutrophils
Bibliographic record
Abstract
Circulating human neutrophils (PMN) die rapidly and their survival is contingent upon rescue from programmed cell death by signals from the inflammatory environment. Diminution of cell volume during apoptosis is closely linked to loss of intracellular K+. We investigated whether prevention of K+ efflux could affect the constitutively active apoptotic machinery. Culture of isolated human PMN in media containing KCl (10–120 mM) attenuated K+ efflux, suppressed apoptosis (assessed by annexin V binding and nuclear DNA content) and prolonged survival within 24–48 h of culture. KCl did not evoke phosphorylation of ERK and Akt, nor did inhibitors of these pathways render PMN insensitive to the anti‐apoptotic actions of KCl. Inhibition of K+ efflux effectively attenuated collapse in mitochondrial transmembrane potential and mitochondrial cytochrome c release, resulting in decreased caspase‐3 activity. Co‐treatment of PMN with KCl and the pan‐caspase inhibitor Z‐VAD‐FMK (20 μM) resulted in slightly greater suppression of apoptosis than KCL alone, suggesting the involvement of mechanism(s) other than inhibition of caspase‐3. Our results indicate that inhibition of K+ efflux promote PMN survival by suppressing apoptosis through preventing mitochondrial dysfunction independent of ERK and phosphatidylinositol 3‐kinase. Thus, K+ released locally from damaged cells may function as a survival signal for PMN, leading to amplification of neutrophil‐mediated tissue injury (Supported by CIHR).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".