Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes.
The expression of angiotensin-I converting enzyme (ACE; EC 3.4.15.1) in human circulating mononuclear cells was studied. T-lymphocytes contained the highest level of enzyme, approx. 28 times more per cell than monocytes. No activity was detected in B-lymphocytes. ACE was present mainly in the microsomal fraction, where it was found to be the major membrane-bound bradykinin-inactivating enzyme. An mRNA for ACE was detected and characterized after reverse transcription and amplification by PCR in T-lymphocytes and several T-cell leukaemia cell lines. We have previously observed that the interindividual variability in the levels of ACE in plasma is, in part, genetically determined and influenced by an insertion/deletion polymorphism of the ACE gene. To investigate the mechanisms involved in the regulation of ACE biosynthesis, the ACE levels of T-lymphocytes from 35 healthy subjects having different ACE genotypes were studied. These levels varied widely between individuals but were highly reproducible and influenced by the polymorphism of the ACE gene. T-lymphocyte levels of ACE were significantly higher in subjects who were homozygote for the deletion than in the other subjects. These results show that ACE is expressed in T-lymphocytes and indicate that the level of ACE expression in cells synthesizing the enzyme is genetically determined.
Costerousse
O
O
Institut National de la Santé et de la Recherche Médicale (INSERM) U367, Paris, France.
Allegrini
J
J
Lopez
M
M
Alhenc-Gelas
F
F
D000328:Adult; D001402:B-Lymphocytes / Q000201:enzymology; D001483:Base Sequence; D001920:Bradykinin / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D015870:Gene Expression; D005838:Genotype; D004854:Herpesvirus 4, Human; D006801:Humans; D006868:Hydrolysis; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008264:Macrophages / Q000201:enzymology; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000097:blood; D013601:T-Lymphocytes / Q000201:enzymology*
D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin