INFLUENCE OF ADENOSINE-DEAMINASE INHIBITION ON THE PHOSPHOINOSITIDE TURNOVER IN THE INITIAL-STAGES OF HUMAN T-CELL ACTIVATION

被引:11
作者
BUC, HA [1 ]
MONCION, A [1 ]
HAMET, M [1 ]
HOULLIER, AM [1 ]
THUILIER, L [1 ]
PERIGNON, JL [1 ]
机构
[1] INSERM,U132,F-75005 PARIS,FRANCE
关键词
D O I
10.1002/eji.1830200322
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
An experimental model of adenosine deaminase deficiency was established on the human T cell line Jurkat by using 2'‐deoxycoformycin, a strong specific inhibitor of the enzyme. When deoxyadenosine was added to the inhibited cells, the nucleotide profile was modified reproducing that found in lymphocytes from adenosine deaminase‐deficient children. The metabolism of phosphoinositides, analyzed by either the release of [3H]inositol phosphates or the breakdown of 32P‐prelabeled phosphatidyl inositides, was compared in normal and modified cells where dATP was accumulated. No modification in 32P labeling of phosphoinositides was detectable within the 32P‐loading period. However, when the cells were stimulated by phytohemagglutinin or anti‐CD3 monoclonal antibody, the phosphoinositide hydrolysis was strongly reduced in the dATP‐containing lymphoblasts. This decrease was correlated with the intracellular dATP concentration. Copyright © 1990 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim
引用
收藏
页码:611 / 615
页数:5
相关论文
共 17 条
[1]   TIGHT-BINDING INHIBITORS .4. INHIBITION OF ADENOSINE DEAMINASES BY VARIOUS INHIBITORS [J].
AGARWAL, RP ;
SPECTOR, T ;
PARKS, RE .
BIOCHEMICAL PHARMACOLOGY, 1977, 26 (05) :359-367
[2]   MECHANISM OF DEOXYADENOSINE-INDUCED CATABOLISM OF ADENINE RIBONUCLEOTIDES IN ADENOSINE DEAMINASE-INHIBITED HUMAN T-LYMPHOBLASTOID CELLS [J].
BAGNARA, AS ;
HERSHFIELD, MS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (08) :2673-2677
[3]  
BARANKIEWICZ J, 1984, J BIOL CHEM, V259, P5178
[5]   DEOXYADENOSINE TRIPHOSPHATE AS A POTENTIALLY TOXIC METABOLITE IN ADENOSINE-DEAMINASE DEFICIENCY [J].
COHEN, A ;
HIRSCHHORN, R ;
HOROWITZ, SD ;
RUBINSTEIN, A ;
POLMAR, SH ;
HONG, R ;
MARTIN, DW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1978, 75 (01) :472-476
[6]  
COLEMAN MS, 1978, J BIOL CHEM, V253, P1619
[7]   OVERPRODUCTION OF ADENINE DEOXYNUCLEOSIDES AND DEOXYNUCLEOTIDES IN ADENOSINE-DEAMINASE DEFICIENCY WITH SEVERE COMBINED IMMUNODEFICIENCY DISEASE [J].
DONOFRIO, J ;
COLEMAN, MS ;
HUTTON, JJ ;
DAOUD, A ;
LAMPKIN, B ;
DYMINSKI, J .
JOURNAL OF CLINICAL INVESTIGATION, 1978, 62 (04) :884-887
[8]   PLASMA DEOXYADENOSINE, ADENOSINE, AND ERYTHROCYTE DEOXYATP ARE ELEVATED AT BIRTH IN AN ADENOSINE DEAMINASE-DEFICIENT CHILD [J].
HIRSCHHORN, R ;
ROEGNER, V ;
RUBINSTEIN, A ;
PAPAGEORGIOU, P .
JOURNAL OF CLINICAL INVESTIGATION, 1980, 65 (03) :768-771
[9]   BIOCHEMICAL AND FUNCTIONAL ABNORMALITIES IN LYMPHOCYTES FROM AN ADENOSINE DEAMINASE-DEFICIENT PATIENT DURING ENZYME REPLACEMENT THERAPY [J].
HUTTON, JJ ;
WIGINTON, DA ;
COLEMAN, MS ;
FULLER, SA ;
LIMOUZE, S ;
LAMPKIN, BC .
JOURNAL OF CLINICAL INVESTIGATION, 1981, 68 (02) :413-421
[10]   TRANSMEMBRANE SIGNALING BY THE T-CELL ANTIGEN RECEPTOR - PERTURBATION OF THE T3-ANTIGEN RECEPTOR COMPLEX GENERATES INOSITOL PHOSPHATES AND RELEASES CALCIUM-IONS FROM INTRACELLULAR STORES [J].
IMBODEN, JB ;
STOBO, JD .
JOURNAL OF EXPERIMENTAL MEDICINE, 1985, 161 (03) :446-456