Cyclic nucleotide phosphodiesterase isoenzyme activities in human alveolar macrophages.
BACKGROUND
Alveolar macrophages and their precursors, the monocytes are involved in airway inflammation in asthma. An increase in intracellular cAMP by PDE inhibitors is known to suppress macrophage and monocyte functions. A comparison of the PDE-isoenzyme 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 III-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.


CONCLUSIONS
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.
Immunopharmacology Group, University of Southampton, UK.
H
H
Tenor
A
A
Hatzelmann
R
R
Kupferschmidt
L
L
Stanciu
R
R
Djukanović
C
C
Schudt
A
A
Wendel
M K
MK
Church
J K
JK
Shute
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D001249:Asthma / Q000201:enzymology; D002454:Cell Differentiation; D002478:Cells, Cultured; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D006868:Hydrolysis; D006969:Hypersensitivity, Immediate / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000201:enzymology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D013379:Substrate Specificity
D007527:Isoenzymes; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D015106:3',5'-Cyclic-GMP Phosphodiesterases