Demonstration of organic anion transport in T lymphocytes. L-lactate and fluo-3 are target molecules.
In this paper, we describe for the first time the existence of organic anion transport in T lymphocytes, exemplified by the transmembrane transport of the anions L-lactate and the Ca2+ indicator fluo-3. The transport of either anion was found to be inhibitable by probenecid, a common blocker of organic anion transport. Transport of L-lactate was observed in long-term cultured T cell lines, as well as in freshly ex vivo isolated T cells, and occurred via a saturable, pH-dependent, and stereospecific process. L-Lactate uptake was dependent on the activation state of the T cells, because activation of T cells by Con A strongly enhanced accumulation of L-lactate from the medium. Because L-lactate may be transported bidirectionally through the T cell membrane in vivo, different physiologic roles of L-lactate transport are discussed. L-Lactate uptake may serve as an alternative source of energy in an inflamed, glucose-deficient tissue or may represent a prerequisite for the earlier-published immunoregulatory function of this molecule on T cells. On the other hand, release of L-lactate emerging from glycolysis could be necessary to avoid acidification of the cell. The fact that the Ca2+ indicator fluo-3 is also transported through the cellular membranes of long-term cultured T cells via organic anion transport has important implications for the determination of Ca2+ influx into T cells. Even though the transport of both molecules, L-lactate and fluo-3, represents organic anion transport, evidence is presented that confirms that the respective transport systems are different.
Sommer
F
F
Institute of Clinical Microbiology, University Erlangen-Nürnberg, Germany.
Bischof
S
S
Röllinghoff
M
M
Lohoff
M
M
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D000838:Anions / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011339:Probenecid / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D018800:Thy-1 Antigens / Q000032:analysis; D014966:Xanthenes / Q000378:metabolism*
D000814:Aniline Compounds; D000838:Anions; D005456:Fluorescent Dyes; D007773:Lactates; D018800:Thy-1 Antigens; D014966:Xanthenes; C059715:Fluo-3; D011339:Probenecid