DIFFERENTIAL ACTIVITY OF P-GLYCOPROTEIN IN NORMAL BLOOD LYMPHOCYTE SUBSETS

To better understand the phenomenon of P-glycoprotein (P-170) expressi on we investigated lymphocyte subpopulations for P-170 function in hea lthy volunteers. Studies were based on three-colour flow cytometry inc luding the fluorescent probe rhodamine 123 (Rh123), which is transport ed by P-170. Marked Rh123 efflux was detected in CD8(+) T lymphocytes with CD8(+)/CD45RA(+) T cells (naive cells)showing significantly highe r P-170 activity as compared with CD8(+)/CD45RA(-) cells (P<0.04). Vic e versa, CD8(+)/CD45RO(+) T cells (memory cells) demonstrated less P-1 70 activity than CD8(+)/CD45RO(-) cells (P<004). P-170 function was le ss prominent in CD4(+) T cells, however, Rh123 efflux was higher in th e CD4(+)/CD45RA(+) and CD4(+)/CD45RO(-) subpopulations (P<0.025) corre sponding to the CD8(+) results. Dye efflux differed significantly betw een activated and non-activated CD8+ and CD4(+) as well as CD8(+)/CD11 b(+) and CD8(+)/CD11b(-) T lymphocytes. Since CD16(+) natural killer c ells (NI() expressed the highest level of P-170, the NK cytotoxicity a gainst Cr-51-labelled K562 target cells was assayed in the presence or absence of P-170 inhibitors. NK related cytotoxicity was significantl y reduced in the presence of R-verapamil and dexnigaldipine-HCP in a d ose-dependent manner. The differential expression of P-170 activity in naive and memory T cells together with the reduced NK related cytotox icity in the presence of MDR-modulators suggest a physiological role o f P-170 in immunological functions of these lymphocyte subsets. Conseq uently, the addition of MDR modulators to conventional chemotherapy as a strategy to overcome drug resistance should consider possible adver se immunosuppressive effects.