Intracellular expression of P-170 glycoprotein in peripheral blood mononuclear cell subsets from healthy donors and HIV-infected patients

Background and Objective. P-glycoprotein (P-gp) is a transmembrane efflux pump that actively extrude a variety of unrelated drugs from cancer cells, leading to the so-called multidrug resistance (MDR) phenomenon. However, P-gp has also been found in normal bone marrow and peripheral blood mononuclear cells (PBMC). Recently, the presence of P-glycoprotein in PBMC from human immunodeficiency virus (HIV)-infected patients has also been investigated and e phenotype-associated P-gp expression has been detected. Design and Methods. A total of thirty-eight HIV-1 positive patients with a mean age of 34 years (range, 24-41 years) were studied after an informed consent. Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation on a Ficoll/Hypaque and P-glycoprotein expression was investigated on lymphocyte population by single and double-color immunofluorescence techniques. We investigated: I) both surface and intracellular expression of the P-gp molecule in different PBMC subsets, II) P-gp expression modifications occurring during HIV infection, and III) the effect of HIV-gp120 on the expression of P-gp by T lymphocyte subsets from healthy donors. Results. Our experimental findings indicate that: a) P-gp glycoprotein can be detected on an intracellular level in different PBMC subpopulations (mainly CD8⁺ T lymphocytes, CD16⁺ NK cells and CD14⁺ monocytes); b) this intracellular expression is decreased in specific PBMC subsets (i.e. T-CD8⁺ and NK-CD16⁺) from HIV-infected patients and c) a rearrangement was obtained when CD4⁺ and CD8⁺ from healthy donors were exposed in vitro to the HIV-binding glycoprotein gp120. Interpretation and Conclusions. Our results indicate that P-gp glycoprotein can also be expressed intracellularity and can be rearranged in PBMC subsets from HIV- infected patients.