FK-506 enhances cyclosporine uptake by peripheral blood lymphocytes.

T HE PROCESS of cellular uptake and metabolism of cyclosporine (CsA) is poorly understood. Previously, we have shown that the transport of CsA in blood occurs in association with plasma Iipoproteins,l with low-density lipoprotein (LOL), and with highdensity lipoprotein, each transporting about 32% of the total amount of CsA in blood. This observation raises the possibility that further cellular metabolism of CsA, at least in part, may take place in conjunction with LOL metabolism through its specific, high-affinity cell surface receptor. In this report, we present results of studies that indicate that (1) [lH]_ labeled CsA is taken up, in an apparently specific manner, by peripheral blood lymphocytes (PBL) when incubated with the [lH] CsA-LOL complex; and (2) cellular uptake of [lH] CsA is enhanced when PBL, whether freshly isolated or stimulated with phytohemagglutinin (PHA), are incubated in a medium containing both [lH] CsA and FK506 (FK) in a 1:1 (wt/wt) proportion.