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.
Institut National de la Santé et de la Recherche Médicale (INSERM) U367, Paris, France.
O
O
Costerousse
J
J
Allegrini
M
M
Lopez
F
F
Alhenc-Gelas
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