CHARACTERIZATION AND CONTROL OF EXPRESSION OF CELL-SURFACE ALKALINE PHOSPHODIESTERASE-I ACTIVITY IN RAT MESANGIAL GLOMERULAR CELLS

Membrane-bound nucleotidases and phosphodiesterases are critical regul ators of extracellular nucleic acid processing. We previously demonstr ated that mesangial cell 5'-nucleotidase was an ectoenzyme, the expres sion of which was stimulated by macrophage-secreted products. We show in the present study that rat mesangial cell alkaline phosphodiesteras e I is also an ectoenzyme characterized by a K-m value of 0.41 mM and a V-max of 20.8 nmol min(-1) mg(-1). Treatment of mesangial cells by d examethasone increased alkaline phosphodiesterase I activity in a dose - and time-dependent manner. Maximal increase (x1.5) occurred after tr eatment with 1 mu M dexamethasone for 5 days. Cycloheximide and RU 384 86, a glucocorticoid receptor antagonist, suppressed the dexamethasone -induced increase in alkaline phosphodiesterase I activity. 5'-Nucleot idase activity was not modified by dexamethasone under similar conditi ons of study. In contrast with 5'-nucleotidase, alkaline phosphodieste rase I expression remained unchanged in the presence of macrophage-con ditioned medium or during cocultures of mesangial cells with macrophag es. Interleukin-l, tumor necrosis factor, cyclic adenosine monophospha te 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 glucoco rticoids. They also show that alkaline phosphodiesterase I and 5'-nucl eotidase obey a different regulation.