Age-related changes of the multidrug resistance P-glycoprotein function in normal human peripheral blood T lymphocytes

C.G Machado,A.B Garcia,R.T Calado,R.P Falcão

doi:10.1590/s0100-879x2003001200006

C.G Machado, A.B Garcia + Show 2 more

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https://doi.org/10.1590/s0100-879x2003001200006

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Abstract

The multidrug resistance P-glycoprotein is a transmembrane efflux pump expressed by lymphocytes and is involved in their cytolytic activity. In the present study, we investigated the age-related changes of P-glycoprotein function in normal peripheral blood lymphocytes. Blood samples from 90 normal volunteers (age range, 0 to 86 years) were analyzed. P-glycoprotein function was assessed by the flow cytometric rhodamine 123 assay. P-glycoprotein function was highest in cord blood and progressively declined with age in peripheral blood T CD4+ and CD8+ cells. In contrast, P-glycoprotein function did not vary with age in CD19+ B or CD16+CD56+ natural killer cells. These data suggest that the decline in P-glycoprotein function in T CD4+ and CD8+ lymphocytes as a function of age may contribute to the decrease in T cell cytolytic activity with aging.

Highlights

P-glycoprotein (P-gp), encoded by the MDR1 (ABCB1) gene, is an energy-dependent transmembrane efflux pump for a variety of unrelated hydrophobic amphipathic drugs [1] which actively extrudes toxic compounds from the cell cytoplasm through the plasma membrane
MRK-16 and UCI2 and other drug-pump inhibitors are able to inhibit the transport of interleukin-2 (IL2), IL-4 and interferon-γ in T lymphocytes
Our findings agree with those of Pilarski et al [15], who evaluated 5 newborn, 36 young and 5 elderly subjects and found that, in T CD4+ cells, P-gp functional expression declined with age

Summary

Introduction

P-glycoprotein (P-gp), encoded by the MDR1 (ABCB1) gene, is an energy-dependent transmembrane efflux pump for a variety of unrelated hydrophobic amphipathic drugs [1] which actively extrudes toxic compounds from the cell cytoplasm through the plasma membrane. P-glycoprotein is expressed by different normal tissues [2]. It is found in epithelial cells of the small and large intestine and in the proximal tubules of the kidney, in hepatocytes, pancreas, blood-brain and blood-testis barriers, and in hematopoietic tissue. P-gp is mainly expressed by T, natural killer (NK) and B lymphocytes, as well as stem cells [3,4,5,6]. The blockade of P-gp function by the MRK16 monoclonal antibody inhibits T cell-mediated cytotoxicity. MRK-16 and UCI2 (monoclonal antibodies directed against Pgp) and other drug-pump inhibitors are able to inhibit the transport of interleukin-2 (IL2), IL-4 and interferon-γ in T lymphocytes

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