In vivo and in vitro modulation of MDR molecules in murine thymocytes

• Published in: International immunopharmacology 2006-02, Vol.6 (2), p.204-215
• Main Authors: Leite, Daniela F.P., Echevarria-Lima, Juliana, Salgado, Leonardo T., Capella, Marcia A.M., Calixto, João B., Rumjanek, Vivian M.
• Format: Article
• Language: English
• Subjects: ABCB1; ABCC1; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP-Binding Cassette Transporters - genetics; Biological and medical sciences; Flow Cytometry; Fluorescent Antibody Technique; Genes, MDR - genetics; Indomethacin - pharmacology; Male; Medical sciences; Mice; Mice, Inbred C3H; Modulators; Multidrug resistance; Multidrug Resistance-Associated Proteins - genetics; Pharmacology. Drug treatments; Probenecid - pharmacology; Propionates - pharmacology; Quinolines - pharmacology; Renal Agents - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Rhodamine 123; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Thymocytes; Thymus Gland - cytology; Thymus Gland - drug effects
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2005.08.005

P-glycoprotein (Pgp/ABCB1) and multidrug resistance related protein 1 (MRP1/ABCC1) were first described in multidrug resistant tumor cells. It is presently known that both proteins are also expressed in a variety of normal cells, including lymphocytes. ABCB1 activity has already been detected in subpopulations of murine thymocytes, but there was little information on the expression or activity of ABCC1 in these cells. The present work studied in mice the expression of both proteins by RT-PCR and immunofluorescence. It was possible to identify the presence of ABCB1 and to detect the expression of ABCC1 in these cells. The functional activities of these proteins were also studied in vivo and in vitro measuring the extrusion of fluorescent dyes in association with MDR modulators. Cyclosporine A, verapamil and trifluoperazine inhibited the activity of thymic ABCB1. Indomethacin, probenecid and MK571 were effective in inhibiting ABCC1 activity by thymic cells. ABCB1 was only active in a small percentage of thymocytes being present in the immature double negative (not CD4 nor CD8) subpopulation and the mature single positive (CD4 or CD8) subpopulations. The functional activity of ABCC1, on the other hand, was more homogeneously distributed being found in all thymocyte subpopulations. Possible physiological roles for these transporters on thymocytes are discussed.