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Expression and activity of the multidrug resistance P-glycoprotein in human
peripheral blood lymphocytes [see comments]
PM Chaudhary, EB Mechetner and IB Roninson
Department of Genetics, University of Illinois, Chicago 60612.
P-glycoprotein (P-gp), the product of the MDR1 (multidrug resistance) gene,
is a transmembrane efflux pump for different lipophilic compounds,
including many anticancer drugs and fluorescent dyes. We have previously
reported that the efflux of fluorescent dyes from lymphoid cells of human
bone marrow was directly correlated with the cellular P-gp content. In the
present study, we show that human peripheral blood lymphocytes (PBL) also
express P-gp, and that P-gp expression correlates with the efflux of
fluorescent dyes from PBL. This efflux was suppressed not only by chemical
inhibitors of P-gp but also by a P-gp-specific monoclonal antibody UIC2,
thus providing direct evidence that it was mediated by P-gp. We have also
characterized dye efflux and UIC2 reactivity in specific PBL subsets. P-gp
was expressed in the majority of CD56+, CD8+, and CD20+ lymphocytes, but in
less than one half of CD4+ cells. P-gp-mediated dye efflux was highly
heterogeneous relative to the expression of CD56RA, CD56RO, Leu-8, and
HLA-DR antigens. No significant P-gp activity was detectable in CD14+
monocytes. MDR1 expression in normal lymphocytes may be a determinant of
multidrug resistance in the corresponding malignancies.
Volume 80,
Issue 11,
pp. 2735-2739,
12/01/1992
Copyright © 1992 by The American Society of Hematology
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