| Abstract |
The association of multidrug resistance (MDR) with resistance to lysis by
natural killer (NK) and lymphokine-activated killer (LAK) cells is
controversial. To address this issue further, drug-resistant variants of a
human Burkitt lymphoma cell line (RAJI) were developed in vitro by
intermittent exposure to adriamycin (R/ADR) or to etoposide (R/VP-16).
The RAJI cell line was selected because it is a standard LAK-susceptible
target. Both MDR lines as well as the parent cell line were found to be
resistant to NK-mediated lysis, but highly susceptible to LAK-mediated
lysis. Notably, R/ADR cells, which express high levels of P-glycoprotein
(P-gp), were nearly eight-times more susceptible to LAK-mediated lysis
than parental cells, whereas R/VP-16 cells, which are P-gp-negative, were
equally as susceptible as parental cells. Immunofluorescence analyses
revealed that expression of cellular adhesion molecules that have been
reported to control susceptibility of targets to NK-and LAK-lysis (ICAM-1,
LFA-1, LFA-3, and MHC class I) did not differ significantly between the
RAJI parent line and drug-resistant variants. This finding suggests that
the increased LAK-sensitivity of R/ADR results from alterations which
affect postbinding stages of the LAK lytic pathway.
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