Selective adenosine release from human B but not T lymphoid cell line.
Intracellular adenosine formation and release to extracellular space was studied in WI-L2-B and SupT1-T lymphoblasts under conditions which induce or do not induce ATP catabolism. Under induced conditions, B lymphoblasts but not T lymphoblasts, release significant amounts of adenosine, which are markedly elevated by adenosine deaminase inhibitors. In T lymphoblasts, under induced conditions, only simultaneous inhibition of both adenosine deaminase activity and adenosine kinase activities resulted in small amounts of adenosine release. Under noninduced conditions, neither B nor T lymphoblasts release adenosine, even in the presence of both adenosine deaminase or adenosine kinase inhibitors. Comparison of B and T cell's enzyme activities involved in adenosine metabolism showed similar activity of AMP deaminase, but the activities of AMP-5'-nucleotidase, adenosine kinase and adenosine deaminase differ significantly. B lymphoblasts release adenosine because of their combination of enzyme activities which produce or utilize adenosine (high AMP-5'-nucleotidase and relatively low adenosine kinase and adenosine deaminase activities). Accelerated ATP degradation in B lymphoblasts proceeds not only via AMP deamination, but also via AMP dephosphorylation into adenosine but its less efficient intracellular utilization results in the release of adenosine from these cells. In contrast, T lymphoblasts release far less adenosine, because they contain relatively low AMP-5'-nucleotidase and high adenosine kinase and adenosine deaminase activities. In T lymphoblasts, AMP formed during ATP degradation is not readily dephosphorylated to adenosine but mainly deaminated to IMP by AMP deaminase. Any adenosine formed intracellularly in T lymphoblasts is likely to be efficiently salvaged back to AMP by an active adenosine kinase. In general, these results may suggest that adenosine can be produced only by selective cells (adenosine producers) whereas other cells with enzyme combination similar to SupT1-T lymphoblasts can not produce significant amounts of adenosine even in stress conditions.
Gensia Pharmaceuticals, Inc., San Diego, California 92121.
J
J
Barankiewicz
G
G
Ronlov
R
R
Jimenez
H E
HE
Gruber
D000241:Adenosine / Q000378:metabolism*; D000248:Adenosine Kinase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D003847:Deoxyglucose / Q000494:pharmacology; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D015649:Pentostatin / Q000494:pharmacology; D051381:Rats; D013601:T-Lymphocytes / Q000378:metabolism*; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology
D007042:Hypoxanthines; C034214:5-iodotubercidin; D019271:Hypoxanthine; D015649:Pentostatin; D007288:Inosine; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D000248:Adenosine Kinase; D000241:Adenosine; D014372:Tubercidin