Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Adrenergic alpha-Antagonists / metabolism
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Aniline Compounds
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Animals
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Antineoplastic Agents / metabolism
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Antineoplastic Agents, Phytogenic / metabolism
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B-Lymphocytes / metabolism
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Calcium Channel Blockers / metabolism
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Fluoresceins
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Fluorescent Dyes / metabolism
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Lymphocytes / metabolism*
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Mice
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Mice, Knockout
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Mitoxantrone / metabolism
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Multidrug Resistance-Associated Proteins / genetics
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Multidrug Resistance-Associated Proteins / metabolism
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Paclitaxel / metabolism
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Prazosin / metabolism
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes / metabolism
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Verapamil / metabolism
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Xanthenes
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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Abcg2 protein, rat
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Adrenergic alpha-Antagonists
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Aniline Compounds
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Antineoplastic Agents
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Antineoplastic Agents, Phytogenic
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Calcium Channel Blockers
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Fluo 4
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Fluoresceins
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Fluorescent Dyes
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Multidrug Resistance-Associated Proteins
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RNA, Messenger
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Xanthenes
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calcein AM
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Mitoxantrone
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Verapamil
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Paclitaxel
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Prazosin
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multidrug resistance-associated protein 1