Multidrug transporter activity in lymphocytes.
Multidrug transporters play a dual role in haematopoietic cells, mediating the efflux of xenobiotics and regulating cell migration. For several reasons including the lack of specific antibodies, reports of multidrug transporter distribution on lymphocytes conflict. Murine B cells have been reported to completely lack transporter activity. Through analysis of parental and 'knockout' mice we show that, contrary to previous studies, murine B and T lymphocytes possess at least three active multidrug transporters and also a hitherto unrecognised drug-specific import activity. Surprisingly, the drug specificity of P-glycoprotein appears cell type dependent. The data indicate that a range of developmentally regulated, multidrug transporters can impose a barrier to treatment of immune disorders.
Elliott
James I
JI
Membrane Transport Biology Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Rd, London W12 0NN, UK. james.elliot@csc.mrc.ac.uk
Raguz
Selina
S
Higgins
Christopher F
CF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000814:Aniline Compounds; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008942:Mitoxantrone / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D014700:Verapamil / Q000378:metabolism; D014966:Xanthenes
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000317:Adrenergic alpha-Antagonists; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D002121:Calcium Channel Blockers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008942:Mitoxantrone; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D011224:Prazosin; D012333:RNA, Messenger; D014700:Verapamil; D014966:Xanthenes; C489249:Abcg2 protein, rat; C409648:Fluo 4; C085925:calcein AM; C421109:multidrug resistance-associated protein 1