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Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

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The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...

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Updated: Mar 17, 2026

An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization

An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization

Published on: June 12, 2013

Alterations in P-Glycoprotein Expression and Function Between Macrophage Subsets.

Theodore J Cory¹, Hui He², Lee C Winchester³

¹Department of Clinical Pharmacy, University of Tennessee Health Science Center College of Pharmacy, Memphis, Tennessee, 38163, USA. tcory1@uthsc.edu.

Pharmaceutical Research

|July 20, 2016

Summary

This summary is machine-generated.

HIV drug concentrations differ between M1 and M2 macrophages due to P-glycoprotein (PGP) variations. M1 cells show higher intracellular lopinavir, while M2 macrophages exhibit greater PGP function and expression, impacting HIV persistence.

Keywords:

Hoechst 33342 P-glycoprotein alternatively activated macrophage classically activated macrophage

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Published on: September 9, 2014

Area of Science:

Immunology
Pharmacology
Virology

Background:

Macrophages are key reservoirs for HIV.
Two main macrophage subsets exist: pro-inflammatory M1 and anti-inflammatory M2.
The distinct roles of M1 and M2 macrophages in HIV pathogenesis are not fully understood.

Purpose of the Study:

To investigate differences in drug efflux transporter expression between M1 and M2 macrophage subsets.
To determine if these differences affect intracellular drug concentrations, specifically for HIV medications.

Main Methods:

U937 monocytic cells were differentiated into M1 or M2 phenotypes.
P-glycoprotein (PGP) function was measured using Hoechst 33342.
PGP expression was analyzed by western blotting.
Intracellular lopinavir concentrations were quantified using LC-MS/MS.
Experiments were validated using primary human monocyte-derived macrophages.

Main Results:

M1 macrophages had significantly higher intracellular concentrations of lopinavir, an antiretroviral drug.
M2 macrophages demonstrated increased PGP function and expression compared to M1 cells.
These findings were consistent in both cell lines and primary macrophages.

Conclusions:

Significant differences in P-glycoprotein expression exist between M1 and M2 macrophages.
These transporter differences can alter intracellular antiretroviral drug concentrations.
Variations in drug concentrations may contribute to persistent low-level HIV replication in macrophages.