Intracellular expression of P-170 glycoprotein in peripheral blood mononuclear cell subsets from healthy donors and HIV-infected patients.
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 a phenotype-associated P-gp expression has been detected.


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+ lymphocytes from healthy donors were exposed in vitro to the HIV-binding glycoprotein gp120.


CONCLUSIONS
Our results indicate that P-gp glycoprotein can also be expressed intracellularly and can be rearranged in PBMC subsets from HIV-infected patients.
Malorni
W
W
Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy. malorni@mclink.it
Lucia
M B
MB
Rainaldi
G
G
Cauda
R
R
Cianfriglia
M
M
Donelli
G
G
Ortona
L
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood*; D000328:Adult; D005260:Female; D015658:HIV Infections / Q000097:blood*; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D008856:Microscopy, Fluorescence
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1