Chemical compounds that target thiol‐disulfide groups on mononuclear phagocytes inhibit immune mediated phagocytosis of red blood cells
Bibliographic record
Abstract
BACKGROUND: Patients having immune cytopenias produce antibodies that target hematopoietic cells resulting in their phagocytosis and intracellular destruction. Early reports suggested that phagocytosis could be inhibited by interfering with membrane thiol (SH) groups on phagocytes. Thus, whether chemical compounds that interact with SH or disulfide (SS) groups on mononuclear phagocytes can inhibit phagocytosis of antibody-coated cells was examined. STUDY DESIGN AND METHODS: A monocyte monolayer assay (MMA), which examines the in vitro monocyte-macrophage (Mphi) interaction with anti-Rh(D)-coated red cells (RBCs), was used to study the ability of different SH and SS chemicals to inhibit the Fc receptor-mediated phagocytosis of sensitized RBCs. The compounds examined included thimerosal, dithiothreitol (DTT), pentane-1-thiol, and two recently described SH and two SS chemicals that have been synthesized. RESULTS: All compounds were found to be able to inhibit phagocytosis to varying degrees correlating to the structure of the molecule. In general, those compounds that interact with free SH groups to inhibit phagocytosis were found better than SH-containing compounds that interact with SSs. Thimerosal and p-nitrophenyl methyl disulfide were the most effective compounds inhibiting phagocytosis. Both chemicals showed greater than 50 percent inhibition at concentrations as low as 10(-9) mol per L. DTT was the least effective compound tested. Only thimerosal showed significant toxicity, as determined by decreased cell viability and increased apoptosis, but only at concentrations of 10(-8) mol per L. The effect of chemical treatment was on attachment rather than on phagocytosis itself. Fcgamma receptor-independent endocytosis was not affected by the chemical treatment. CONCLUSION: These studies indicate that pharmacologic strategies that target SH groups on mononuclear phagocytes may have future efficacy for the treatment of immune cytopenias.
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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".