MOLECULAR AND GENETIC-ASPECTS OF DIPEPTIDYL CARBOXYPEPTIDASE-I (THE ANGIOTENSIN-I CONVERTING-ENZYME) - EXPRESSION IN THE IMMUNE-SYSTEM

The angiotensin I converting enzyme (ACE) is an ectoenzyme of vascular endothelial cells, also secreted in plasma, that plays an important r ole in cardiovascular homeostasis through vasoactive peptide metabolis m. It is also synthetized in several other cell types, including macro phages and T lymphocytes. ACE is a peculiar peptidase resulting from a n ancestral gene duplication and possesses two active sites in a singl e polypeptide chain. These two active sites do not have exactly the sa me structure and may have a different substrate specificity in vivo, a lthough they both cleave angiotensin I, bradykinin and substance P. AC E gene expression in man displays a genetic polymorphism. Both the lev el of 'soluble' ACE in plasma and of membrane bound ACE in lymphocytes are genetically determined. ACE synthesis and secretion increase dram atically during monocyte and macrophage activation and in granulomatou s diseases involving activated macrophages such as sarcoidosis. ACE ge ne expression is also activated in mature T lymphocytes. The function( s) of ACE in the immune system remain unknown but could be related to the metabolism of peptides participating in the inflammatory response and perhaps also to the proteolytic processing involved in antigen rec ognition.