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Cyclic AMP and cyclic GMP phosphodiesterase activities in Hodgkin's disease lymphocytes
Insights
Patients with Hodgkin
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Hodgkin's disease (HD) is a cancer of the lymphatic system.
- Lymphocyte cyclic nucleotide levels are altered in HD patients.
- Cyclic nucleotide phosphodiesterase (PDE) enzymes regulate cyclic nucleotide levels.
Purpose of the Study:
- To investigate cyclic nucleotide phosphodiesterase (PDE) activities in lymphocytes from Hodgkin's disease patients.
- To determine if altered PDE activity contributes to abnormal cyclic nucleotide levels in HD.
Main Methods:
- Studied PDE activities in peripheral blood monocyte-depleted lymphocytes and T-lymphocyte suspensions.
- Compared enzyme activities between thirteen untreated HD patients and fourteen healthy volunteers.
- Assessed PDE activity in the presence and absence of calmodulin and calcium.
Main Results:
- Monocyte-depleted lymphocytes from HD patients exhibited twofold higher PDE activities than controls.
- T-lymphocyte suspensions from HD patients showed fourfold higher cAMP-PDE and threefold higher cGMP-PDE activities.
- PDE hydrolytic activities were unaffected by calmodulin and calcium in both groups.
Conclusions:
- Elevated PDE activities in lymphocytes may be responsible for altered cyclic nucleotide levels in Hodgkin's disease.
- These findings highlight the role of PDE dysregulation in the immunodeficiency associated with HD.
Abstract:
Cyclic nucleotide phosphodiesterase (PDE) activities were studied in peripheral blood monocyte-depleted lymphocytes and enriched T-lymphocyte suspensions from thirteen patients with previously untreated Hodgkin's disease (HD) and fourteen age and sex matched healthy volunteers. Monocyte-depleted lymphocytes from HD patients showed PDE-activities which were two times higher than in their normal counterpart cells. The mean cAMP-PDE activity present in enriched HD T-lymphocyte suspensions was four times higher than in control T-lymphocytes, and the mean cGMP-PDE associated with HD T-lymphocytes was three times higher than in the controls. The hydrolytic activities present in both monocyte-depleted and T-lymphocyte enriched cells suspensions remained unchanged in absence or in the presence of calmodulin and calcium. Since depressed cAMP and cGMP resting levels have been observed in HD lymphocytes and lymphocyte subpopulations, our results suggest that the elevated PDE activities are, at least in part, responsible for the alterations in lymphocyte cyclic nucleotide levels.