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Evidence to suggest that the phosphodiesterase 4 isoenzyme is present and involved in the proliferation of umbilical cord blood mononuclear cells

Authors


Banner Pfizer Central Research, Discovery Biology, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.

Abstract

Background

The type 4 phosphodiesterase (PDE) isoenzyme is the main isoenzyme of PDE involved in the control of adult mononuclear cell proliferation.

Objective

To establish whether PDE isoenzymes are present in umbilical cord blood mononuclear cells by the use of selective PDE inhibitors, and to identify which PDE isoenzymes are involved in controlling the proliferation of cord blood mononuclear cells.

Methods

Cord blood was obtained from normal deliveries and mononuclear cells isolated as described previously [ 1] with some modifications. Mononuclear cells were then stimulated to proliferate with phytohaemagglutinin (PHA) (2 μg/mL) in the presence of selective PDE inhibitors. Proliferation was measured by [3H]-thymidine incorporation.

Results

The type 4 PDE inhibitors (CDP840, rolipram and RO 20-1724), and the mixed PDE3/4 inhibitor, zardaverine, produced a concentration-related inhibition of PHA-stimulated cord blood mononuclear cell proliferation (P < 0.05, anova). The non-selective PDE inhibitor, theophylline, also produced a concentration-related inhibition of proliferation (P < 0.05, anova). In contrast, the PDE1 inhibitor, vinpocetine, the PDE3 inhibitor, siguazodan, and the PDE5 inhibitor, zaprinast, were unable to inhibit cord blood mononuclear cell proliferation.

Conclusion

PDE4 is present in umbilical cord mononuclear cells and is involved in the control of cord blood mononuclear cell proliferation.

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