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 eff lux pump that actively extrude a variety of unrelated drugs from cance r cells, leading to the so-called multidrug resistance (MDR) phenomeno n. However, P-gp has also been found in normal bone marrow and periphe ral blood mononuclear cells (PBMC). Recently, the presence of P-glycop rotein in PBMC from human immunodeficiency virus (HIV)-infected patien ts has also been investigated and a phenotype-associated P-gp expressi on 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) w ere studied after an inform ed consent. Peripheral blood mononuclear c ells (PBMC) were isolated by centrifugation on a Ficoll/Hypaque and P- glycoprotein expression was investigated on lymphocyte population by s ingle 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 du ring HIV infection, and iii) the effect of HIV-gp120 on the expression of P-gp by T lymphocyte subsets from healthy donors. Results. Our exp erimental findings indicate that: a) P-gp glycoprotein can be detected on an intracellular level in different PBMC subpopulations (mainly CD 8(+) 7 lymphocytes, CD16(+) NK cells and CD14(+) monocytes); b) this i ntracellular expression is decreased in specific PBMC subsets (i.e. T- CD8(+) and NK-CD16(+)) from HIV-infected patients and c) a rearrangeme nt was obtained when CD4(+) and CD8(+) lymphocytes from healthy donors were exposed in vitro to the HIV-binding glycoprotein gp120. Interpre tation and Conclusions. Our results indicate that P-gp glycoprotein ca n also be expressed intracellularly and can be rearranged in PBMC subs ets from HIV-infected patients. (C) 1998, Ferrata Storti Foundation.