Cyclosporine-induced adenosine triphosphate depletion in murine T and B lymphocytes.
Adenosine metabolism in C57BL/6 mouse spleen cells was studied. Adenosine triphosphate (ATP) levels in resting T cells were 26.9 +/- 3.4 ng/10(5) cells compared with 16.5 +/- 3.1 ng/10(5) cells in resting B cells. Cyclosporine (CSA) caused a prompt and severe ATP depletion in both T and B cells, which could be mitigated by the addition of adenosine. B cell ATP levels were returned to normal while T cell levels were only partially restored. The adenosine deaminase inhibitor erythro-9-(2 hydroxy-3 nonyl) adenine (EHNA) also caused ATP depletion in T and B cells, which could similarly be prevented in part by the addition of adenosine. However, when CSA and EHNA were combined, adenosine could no longer protect ATP pools and severe ATP depletion in T and B cells occurred. This suggests that CSA and EHNA affect different steps in the conversion of adenosine to ATP. Although both T and B cell ATP levels were affected by CSA, the ability of supplementary substrate to restore ATP levels to normal in B cells but not in T cells may explain the apparent selective effect of CSA impairing T cell functions with sparing of B cell functions. Furthermore, if causing ATP depletion is associated with immunosuppressive activity, EHNA may be useful in potentiating the immunosuppressive effects of CSA.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D058892:Adenosine Deaminase Inhibitors; D003524:Cyclosporins; C010192:9-(2-hydroxy-3-nonyl)adenine; D000255:Adenosine Triphosphate; D000225:Adenine; D000241:Adenosine