Release of Anti‐HIV Mediators after Administration of Leukotriene B<sub>4</sub>to Humans
Bibliographic record
Abstract
BACKGROUND: CD8(+) T cells can control human immunodeficiency virus (HIV) through the lysis of infected cells and the release of soluble mediators, such as macrophage inflammatory protein (MIP)-1 beta, which prevent entry of HIV and/or inhibit HIV replication. Because neutrophils represent a major source of alpha-defensins and, to a lesser extent, MIP-1 beta, we determined whether leukotriene B(4) (LTB(4)), a potent neutrophil agonist, would trigger the release of these 2 anti-HIV peptides. METHODS: Plasma samples from HIV-uninfected subjects receiving intravenous bolus of LTB(4) were analyzed for alpha-defensins and MIP-1 beta levels by use of enzyme-linked immunosorbent assay. Furthermore, in vitro analysis of intracellular and secreted levels of alpha-defensins of resting and LTB(4)-activated neutrophils from HIV-uninfected and HIV-infected subjects were determined. LTB(4) modulation of CD63 and CD66b markers associated with degranulation were studied by use of flow cytometry. Chemotaxis of neutrophils from HIV-uninfected and HIV-infected subjects toward LTB(4) or interleukin (IL)-8 was determined by use of migration assays. RESULTS: Administration of LTB(4) to humans caused a dose-dependent plasmatic increase in alpha-defensins and MIP-1 beta proteins, with peak levels observed 2 h after administration of LTB(4). Neutrophils isolated from HIV-infected and HIV-uninfected subjects contained similar levels of stored alpha-defensins that were effectively secreted in vitro, in response to LTB(4) activation. Chemotaxis of neutrophils toward LTB(4) or IL-8 was identical among the groups of subjects. CONCLUSION: LTB(4) induced the secretion alpha-defensins and MIP-1 beta. Neutrophils from HIV-infected subjects were fully responsive to LTB(4), which highlights a potential usefulness of this lipid mediator in the management of HIV infection.
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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".