Characteristics of monocyte angiotensin-converting enzyme (ACE) induction by dexamethasone.
Monocyte maturation to macrophages and transformation into epithelioid granuloma cells in some granulomatous diseases are accompanied by the induction of membrane-bound angiotensin-converting enzyme (ACE). The physiologic and pathophysiologic roles of ACE generated in these processes are not known. The pattern and the mechanism of ACE induction in human monocytes are also not well understood. Dexamethasone is one of the agents reported to induce elevated ACE activity in human monocytes, and therefore a suitable tool for studying the phenomenon. This study shows that dexamethasone augments monocyte ACE in a biphasic dose-dependent manner with maximum effect at 10(-8) M concentration. Although it enhances the level of ACE activity, dexamethasone does not alter the time course for ACE induction from that found in unstimulated monocytes. The ACE activity of monocytes cultivated in 10 nM dexamethasone and then exposed to 10(-3) M diazosulfanilic acid (DASA) is reduced approximately by 80% in comparison with cells not treated with DASA, demonstrating that dexamethasone-induced ACE is an ectoenzyme. Dexamethasone does not increase the activity of other monocyte ectoenzymes: gamma-glutamyltransferase, alkaline phosphodiesterase-I, and leucine aminopeptidase, showing that dexamethasone induction of ACE is a specific, rather than generalized, effect on plasma membrane enzymes. It is suggested that the increase in ACE activity is due to the increased rate of enzyme synthesis.
Vuk-Pavlović
Z
Z
Thoracic Diseases Research Unit, Mayo Clinic/Foundation, Rochester, Minnesota 55905.
Kreofsky
T J
TJ
Rohrbach
M S
MS
D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D009000:Monocytes / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*; D013997:Time Factors
D003907:Dexamethasone; D007703:Peptidyl-Dipeptidase A