Preferential expression and activity of multidrug resistance gene 1 product (P-glycoprotein), a functionally active efflux pump, in human CD8 + T cells: A role in cytotoxic effector function

1992 ◽  
Vol 12 (6) ◽  
pp. 451-458 ◽  
Author(s):  
Sudhir Gupta ◽  
Choong H. Kim ◽  
Takashi Tsuruo ◽  
Sastry Gollapudi
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Efflux Pump ◽  
Multidrug Resistance Gene ◽  
Active Efflux ◽  
Preferential Expression ◽  
P Glycoprotein ◽  
Active Efflux Pump ◽  
Cytotoxic Effector ◽  
Expression And Activity

P-glycoprotein efflux pump expression and activity in Calu-3 cells

2001 ◽  
Vol 90 (5) ◽  
pp. 645
Author(s):  
Karen O. Hamilton ◽  
Gunilla Backstrom ◽  
Mehran A. Yazdanian ◽  
Kenneth L. Audus
Keyword(s):  
Efflux Pump ◽  
P Glycoprotein ◽  
Expression And Activity

P-glycoprotein regulates trafficking of CD8+ T cells to the brain parenchyma

2014 ◽  
Vol 127 (5) ◽  
pp. 699-711 ◽  
Author(s):  
Gijs Kooij ◽  
Jeffrey Kroon ◽  
Debayon Paul ◽  
Arie Reijerkerk ◽  
Dirk Geerts ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Brain Parenchyma ◽  
P Glycoprotein ◽  
The Brain

scholarly journals In Situ Biochemical Demonstration That P-Glycoprotein Is a Drug Efflux Pump with Broad Specificity

2000 ◽  
Vol 148 (5) ◽  
pp. 863-870 ◽  
Author(s):  
Yu Chen ◽  
Sanford M. Simon
Keyword(s):  
Fluorescent Protein ◽  
Efflux Pump ◽  
Multiple Drug Resistance ◽  
Living Cells ◽  
Drug Accumulation ◽  
Multiple Drug ◽  
Gfp Expression ◽  
Active Efflux ◽  
P Glycoprotein ◽  
Wide Range

While P-glycoprotein (Pgp) is the most studied protein involved in resistance to anti-cancer drugs, its mechanism of action is still under debate. Studies of Pgp have used cell lines selected with chemotherapeutics which may have developed many mechanisms of resistance. To eliminate the confounding effects of drug selection on understanding the action of Pgp, we studied cells transiently transfected with a Pgp-green fluorescent protein (GFP) fusion protein. This method generated a mixed population of unselected cells with a wide range of Pgp-GFP expression levels and allowed simultaneous measurements of Pgp level and drug accumulation in living cells. The results showed that Pgp-GFP expression was inversely related to the accumulation of chemotherapeutic drugs. The reduction in drug concentration was reversed by agents that block multiple drug resistance (MDR) and by the UIC2 anti-Pgp antibody. Quantitative analysis revealed an inverse linear relationship between the fluorescence of Pgp-GFP and MDR dyes. This suggests that Pgp levels alone limit drug accumulation by active efflux; cooperativity between enzyme, substrate, or inhibitor molecules is not required. Additionally, Pgp-GFP expression did not change cellular pH. Our study demonstrates the value of using GFP fusion proteins for quantitative biochemistry in living cells.

scholarly journals Human CD8 T cells of the peripheral blood contain a low CD8 expressing cytotoxic/effector subpopulation

Immunology ◽  
2003 ◽  
Vol 108 (3) ◽  
pp. 305-312 ◽  
Author(s):  
Axel Trautmann ◽  
Beate Ruckert ◽  
Peter Schmid-Grendelmeier ◽  
Eva Niederer ◽  
Eva-B. Brocker ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cytotoxic Effector

scholarly journals Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia.

1989 ◽  
Vol 9 (10) ◽  
pp. 4357-4363 ◽  
Author(s):  
H Galski ◽  
M Sullivan ◽  
M C Willingham ◽  
K V Chin ◽  
M M Gottesman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multidrug Resistance ◽  
Transgenic Mice ◽  
Bone Marrow Cells ◽  
Efflux Pump ◽  
Multidrug Resistance Gene ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Leukocyte Counts ◽  
Actin Promoter

The human multidrug resistance gene (MDR1) encodes a drug efflux pump glycoprotein (P-glycoprotein) responsible for resistance to multiple cytotoxic drugs. A plasmid carrying a human MDR1 cDNA under the control of a chicken beta-actin promoter was used to generate transgenic mice in which the transgene was mainly expressed in bone marrow and spleen. Immunofluorescence localization studies showed that P-glycoprotein was present on bone marrow cells. Furthermore, leukocyte counts of the transgenic mice treated with daunomycin did not fall, indicating that their bone marrow was resistant to the cytotoxic effect of the drug. Since bone marrow suppression is a major limitation to chemotherapy, these transgenic mice should serve as a model to determine whether higher doses of drugs can cure previously unresponsive cancers.

scholarly journals IPEC-J2 rMdr1a, a New Cell Line with Functional Expression of Rat P-glycoprotein Encoded by Rat Mdr1a for Drug Screening Purposes

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 673 ◽  
Author(s):  
Lasse Saaby ◽  
Josefine Trasborg ◽  
Mikkel A. Rasmussen ◽  
Bjørn Holst ◽  
Birger Brodin
Keyword(s):  
Cell Line ◽  
Efflux Pump ◽  
Cell Model ◽  
Drug Distribution ◽  
Functional Expression ◽  
Established Cell Line ◽  
Multidrug Resistance Gene ◽  
Western Blots ◽  
P Glycoprotein

The efflux pump P-glycoprotein (P-gp) affects drug distribution after absorption in humans and animals. P-gp is encoded by the multidrug resistance gene (MDR1) gene in humans, while rodents (the most common preclinical animal model) express the two isoforms Mdr1a and Mdr1b. Differences in substrate selectivity has also been reported. Our aim was to generate an in vitro cell model with tight barrier properties, expressing functional rat Mdr1a P-gp, as an in vitro tool for investigating species differences. The IPEC-J2 cell line forms extremely tight monolayers and was transfected with a plasmid carrying the rat Mdr1a gene sequence. Expression and P-gp localization at the apical membrane was demonstrated with Western blots and immunocytochemistry. Function of P-gp was shown through digoxin transport experiments in the presence and absence of the P-gp inhibitor zosuquidar. Bidirectional transport experiments across monolayers of the IPEC-J2 rMDR1a cell line and the IPEC-J2 MDR1 cell line, expressing human P-gp, showed comparable magnitude of transport in both the absorptive and efflux direction. We conclude that the newly established IPEC-J2 rMdr1a cell line, in combination with our previously established cell line IPEC-J2 MDR1, has the potential to be a strong in vitro tool to compare P-gp substrate profiles of rat and human P-gp.

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