CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE ISOENZYME ACTIVITIES IN HUMAN ALVEOLAR MACROPHAGES

Background Alveolar macrophages and their precursors, the monocytes ar e involved in airway inflammation in asthma. An increase in intracellu lar cAMP by PDE inhibitors is known to suppress macrophage and monocyt e functions. A comparison of the PDE-isoenzyme profiles of human alveo lar 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 DE i soenzyme 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 inve stigated using isoenzyme selective inhibitors and activators. Results In macrophages substantial PDE I activity, which was significantly hig her than PDE III-V activity was detected and PDE II was absent. PDE II I was membrane-bound whereas PDE I, IV and V were soluble. No differen ce 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 an d alveolar macrophages are distinct targets for the effects of selecti ve PDE inhibitors while alveolar macrophages from normal and atopic in dividuals appear to be equally sensitive.