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Biomedical subjects

A R Tambur

Publications and source records attributed to A R Tambur.

6 recordsLinked to original sources
PubMed1998

IL-4 inhibits P-glycoprotein in normal and malignant NK cells.

Patients presenting with a natural killer (NK) cell leukemia generally have a poor prognosis. NK cell tumors are generally resistant to numerous chemotherapeutic drugs and even combination chemotherapy usually results in only short term remissions. The drug resistance of NK cell leukemias may be at least partially explained by their expression of the multidrug resistant transporter, P-glycoprotein (Pgp). In this study, we demonstrate that the expression and function of Pgp activity on NK cells (leukemic and normal) can be reversed with IL-4.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Differential sensitivity of resting and IL-2 activated NK cells to R-verapamil.

Natural killer (NK) cells are the first lymphoid population to reconstitute the peripheral blood compartment of immunologically compromised bone marrow transplant (BMT) recipients. Recent data suggest that, among patients transplanted for leukemia, NK cells can prevent or delay disease relapse by mediating a cytotoxic graft vs leukemia (GvL) response. Although the major mechanism by which NK cells mediate target cell lysis involves degranulation and release of cytolytic effector molecules (granzymes, proteoglycans, perforin), accumulating evidence suggests that NK cells possess additional pathways to mediate target cell killing. In fact, it is well recognized that recombinant cytokines such as IL-2 enhance the in vitro cytolytic activity of NK cells. In this study, we observed that the lytic activity mediated by resting and IL-2 activated NK cells against the same target cell appears to occur via two distinct pathways, as distinguished by their differential response to R-verapamil. Specifically, we observed that 25 microM R-verapamil inhibited the lytic activity of resting NK cells against K562 targets by approximately 50%. However, the lytic activity of IL-2 activated NK cells was unaffected by this concentration of R-verapamil. Additional studies suggested that the inhibitory effect of R-verapamil on NK cytotoxic activity was associated with its ability to prevent degranulation of cytotoxic granules. Specifically, R-verapamil inhibited BLT esterase release from resting but not IL-2 activated NK cells. These data suggest that IL-2 activated NK cells can promote target cell lysis by a pathway (possibly degranulation independent) distinct from that used by resting NK cells. We speculate that the target of R-verapamil on resting NK cells is P-glycoprotein (Pgp), an ABC transporter that we recently reported was expressed on NK cells and whose functional activity is known to be inhibited by R-verapamil.

ATP Binding Cassette Transporter, Subfamily B, Mem↗