Altered phosphorylation as a possible basic for cyclic nucleotide abnormalities in atopic dermatitis

Exposure of normal mononuclear leukocytes (MNL) to histamine causes heterologous desensitization accompanied by beta adrenergic receptor alterations and increased cyclic AMP-specific phosphodiesterase (PDE) activity. We have demonstrated similar abnormalities in MNL from patients with atopic dermatitis (AD). Considering that these dual changes might be due to altered phosphorylation, we have studied cyclic AMP-dependent protein kinase (PK-A) in untreated and histamine-treated normal MNL and in AD cells. We found that basal or endogenous phosphorylative activity was two-fold higher in preparations from patients with AD. The activity ratios of protein kinase increased significantly in normal MNL after histamine exposure. In contrast, cells from patients with AD failed to show this increase. These findings correlate with similarly increased PDE activity after histamine stimulation of normal, but not AD cells. The increased PK-A activity in both atopic and histamine-desensitized MNL correlates with membrane receptor changes and elevated PDE activity. This enhanced phosphorylation may account for the varied physiological and immunological abnormalities that have been described in AD.