Impairment of SHP-1 down-regulation in the lipid rafts of human neutrophils under GM-CSF stimulation contributes to their age-related, altered functions
Why this work is in the frame
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Bibliographic record
Abstract
It has been shown that the functions and the rescue from apoptosis by proinflammatory mediators of polymorphonuclear leukocytes (PMN) tend to diminish with aging. Here, we investigated the role of protein tyrosine phosphatases (PTP), especially Src homology domain-containing protein tyrosine phosphatase-1 (SHP-1), in the age-related, altered PMN functions under granulocyte macrophage-colony stimulating factor (GM-CSF) stimulation. The inhibition of PTP suggested a differential effect of GM-CSF on phosphatase activity in modulating PMN functions with aging. The down-regulation of phosphatase activity of immunopurified SHP-1 from lipid rafts of PMN of young donors was found significantly altered at 1 min of stimulation with aging. In young donors, SHP-1 is displaced from lipid rafts at 1 min of stimulation, whereas in the elderly, SHP-1 is constantly present. We assessed in PMN lipid rafts the phosphorylation of tyrosine and serine residues of SHP-1, which regulates its activity. We observed an alteration in the phosphorylation of tyrosine and serine residues of SHP-1 in PMN of elderly subjects, suggesting that GM-CSF was unable to inhibit SHP-1 activity by serine phosphorylation. GM-CSF activates Lyn rapidly, and we found alterations in its activation and translocation to the lipid rafts with aging. We also demonstrate that SHP-1 in the PMN of elderly is constantly recruited to Lyn, which cannot be relieved by GM-CSF. In contrast, in the young, the resting recruitment could be relieved by GM-CSF. Our results suggest an alteration of the SHP-1 modulation by GM-CSF in lipid rafts of PMN with aging. These alterations could contribute to the decreased GM-CSF effects on PMN.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 it