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 role in cardiovascular homeostasis through vasoactive peptide metabolism. It is also synthetized in several other cell types, including macrophages and T lymphocytes. ACE is a peculiar peptidase resulting from an ancestral gene duplication and possesses two active sites in a single polypeptide chain. These two active sites do not have exactly the same structure and may have a different substrate specificity in vivo, although they both cleave angiotensin I, bradykinin and substance P. ACE gene expression in man displays a genetic polymorphism. Both the level of 'soluble' ACE in plasma and of membrane bound ACE in lymphocytes are genetically determined. ACE synthesis and secretion increase dramatically during monocyte and macrophage activation and in granulomatous diseases involving activated macrophages such as sarcoidosis. ACE gene 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 recognition.