Characterization and control of expression of cell surface alkaline phosphodiesterase I activity in rat mesangial...

Membrane-bound nucleotidases and phosphodiesterases are critical regulators of extracellular nucleic acid processing. We previously demonstrated that mesangial cell 5'-nucleotidase was an ectoenzyme, the expression of which was stimulated by macrophage-secreted products. We show in the present study that rat mesangial cell alkaline phosphodiesterase I is also an ectoenzyme characterized by a Km value of 0.41 mM and a Vmax of 20.8 nmol min-1 mg-1. Treatment of mesangial cells by dexamethasone increased alkaline phosphodiesterase I activity in a dose- and time-dependent manner. Maximal increase (x1.5) occurred after treatment with 1 microM dexamethasone for 5 days. Cycloheximide and RU 38486, a glucocorticoid receptor antagonist, suppressed the dexamethasone-induced increase in alkaline phosphodiesterase I activity. 5'-Nucleotidase activity was not modified by dexamethasone under similar conditions of study. In contrast with 5'-nucleotidase, alkaline phosphodiesterase I expression remained unchanged in the presence of macrophage-conditioned medium or during cocultures of mesangial cells with macrophages. Interleukin-1, tumor necrosis factor, cyclic adenosine monophosphate and adenosine analogues also activated 5'-nucleotidase whereas they were inactive on alkaline phosphodiesterase I. These results suggest that extracellular DNA trapped in the mesangial area of the glomerular capillaries may be processed in part at the cell surface by alkaline phosphodiesterase I and that such an event may be regulated by glucocorticoids. They also show that alkaline phosphodiesterase I and 5'-nucleotidase obey a different regulation.