Cyclic nucleotide phosphodiesterase isoenzyme activities in human alveolar macrophages
Article first published online: 27 APR 2006
Clinical & Experimental Allergy
Volume 25, Issue 7, pages 625–633, July 1995
How to Cite
TENOR, H., HATZELMANN, A., KUPFERSCHMIDT, R., STANCIU, L., DJUKANOVIC, R., SCHUDT, C., WENDEL, A., CHURCH, M. K. and SHUTE, J. K. (1995), Cyclic nucleotide phosphodiesterase isoenzyme activities in human alveolar macrophages. Clinical & Experimental Allergy, 25: 625–633. doi: 10.1111/j.1365-2222.1995.tb01110.x
- Issue published online: 27 APR 2006
- Article first published online: 27 APR 2006
- Submitted 18 August 1994; revised 9 January 1995; accepted 20 January 1995.
- alveolar macrophages;
Background Alveolar macrophages and their precursors, the monocytes are involved in airway inflammation in asthma. An increase in intraceliular cAMP by PDE inhibitors is known to suppress macrophage and monocyte functions. A comparison of the PDE-isoenzyine profiles of human alveolar macrophages from normal and atopic donors and of human peripheral blood monocytes might form a basis to differentially affect functions of these cells by PDE inhibitors.
Objective The study compares the PDE isoenzyme activity profiles of human alveolar macrophages from normal and atopic asthmatic donors and human peripheral blood monocytes. In addition, the effect of in vitro maturation of monocytes on their PDE isoenzyme profile is studied.
Methods Macrophages were purified (95-97%) by adherence to plastic, and blood monocytes were purified (88%) by counter-current elutriation. PDE isoenzyme activity profiles were investigated using isoenzyme selective inhibitors and activators.
Results In macrophages substantial PDE I activity, which was significantly higher than PDE IIF-V activity was detected and PDE II was absent. PDE III was membrane-bound whereas PDE I, IV and V were soluble. No difference was found between alveolar macrophages of normal donors and atopic asthmatics. Monocytes exclusively contained PDE IV but their in vitro maturation led to a PDE isoenzyme profile similar to that of alveolar macrophages.
Conclusion These results indicate that human monocytes and alveolar macrophages are distinct targets for the effects of selective PDE inhibitors while alveolar macrophages from normal and atopic individuals appear to be equally sensitive.