Monocyte localization of elevated cAMP phosphodiesterase activity in atopic dermatitis.
Patients with atopic dermatitis (AD) manifest a number of immune abnormalities which correlate with in vitro defects including lymphocyte transformation, chemotaxis, and cytotoxicity. Past studies have shown reduced leukocyte cyclic 3',5'-adenosine monophosphate (cAMP) levels after exposure to adenylate cyclase-active agonists, and we have demonstrated that this results from increased catabolism due to elevated cAMP-phosphodiesterase activity. These results were obtained in preparations containing mixtures of lymphocytes and monocytes. In order to determine more precisely the cellular site of the defect we have separated the leukocytes into lymphocyte- and monocyte-enriched preparations using either Percoll-gradient centrifugation or adherence isolation. Both techniques yielded over 93% pure lymphocytes, whereas the former yielded 64% monocytes compared with the latter method which generated 94% pure monocytes. Atopic monocytes, obtained by either technique, consistently showed elevated phosphodiesterase activity compared with those of the nonatopic monocytes. Such differences were not evident in lymphocyte preparations from normal and atopic subjects. In spite of the increased rate of cAMP degradation in atopic leukocytes, the resting cAMP levels do not differ from those of normal subjects. We questioned whether this is caused by increased cAMP synthesis and evaluated cellular adenylate cyclase activity. We found no evidence in AD cells for an increased rate of adenylate cyclase catalysis, either basal activity or after stimulation by forskolin. Therefore, the resting cAMP levels must have been compensated by other mechanisms. Impaired cyclic nucleotide metabolism in atopic monocytes may affect a number of immunologic and inflammatory reactions and could account for many of the clinical abnormalities in atopic diseases.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000097:blood*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D002469:Cell Separation / Q000379:methods; D006801:Humans; D009000:Monocytes / Q000145:classification / Q000201:enzymology*; D011565:Psoriasis / Q000097:blood / Q000201:enzymology*
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases