       Document 0596
 DOCN  M9630596
 TI    Transmembrane P-glycoprotein (P-gp/P-170) in HIV infection: analysis of
       lymphocyte surface expression and drug-unrelated function.
 DT    9603
 AU    Lucia MB; Cauda R; Landay AL; Malorni W; Donelli G; Ortona L; Istituto
       Clinica delle Malattie Infettive, Universita Cattolica; del Sacro Cuore,
       Rome, Italy.
 SO    AIDS Res Hum Retroviruses. 1995 Aug;11(8):893-901. Unique Identifier :
       AIDSLINE MED/96020090
 AB    P-glycoprotein (P-gp/P-170), a transmembrane efflux pump known to be one
       of the mechanisms responsible for multidrug resistance in cancer
       therapy, is constitutively expressed in several solid human tissues as
       well as in normal peripheral blood lymphocytes and bone marrow cells. In
       particular, this molecule has been associated with the transport of
       perforin and other cytolysins in natural killer (NK) and T cytotoxic
       lymphocytes. In the present study, we analyzed peripheral blood
       lymphocytes (PBLs) from controls and HIV+ patients for phenotypic
       expression and function of the P-gp/P-170 molecule. We found that 90% of
       all PBL subsets (i.e., CD4+, CD8+, CD56+, and CD19+ cells) expressed
       surface P-gp/P-170 both in controls and HIV+ patients. However, a
       significant decrease in CD4+/P-170+ and CD19+/P-170+ cells was observed
       in HIV+ individuals with respect to controls. PHA and IL-2 stimulation
       of PBLs was unable to increase the expression of P-gp/P-170 both in
       controls and HIV+ patients, despite the increased detection of the CD25
       molecule. On the other hand, stimulation with anti-CD3 determined a
       significant increase in lymphocyte P-gp/P-170. The function of
       P-gp/P-170, assessed by a flow cytometric assay for rhodamine-123
       (Rh123) efflux, was significantly reduced in CD16+ NK cells and CD19+ B
       cells from HIV+ patients. The Rh123 efflux by NK cells correlated (p <
       0.01) with the NK cytotoxicity against the 51Cr-labeled K562 cell line.
       Last, the effect of the antiretroviral drugs AZT, ddI, and ddC on P-gp
       expression and function was evaluated. The dideoxynucleoside compounds
       did not inhibit P-gp/P-170 function of normal mononuclear cells in
       vitro, and did not increase P-gp/P-170 expression in vivo, in patients
       undergoing antiretroviral therapy with AZT. These findings provide
       further evidence of a possible involvement of the P-gp/P-170 system in
       specific immunological lymphocyte functions, and especially in
       cytotoxic-type functions. In addition, it is possible to suggest, on the
       basis of our experimental data, that the dideoxynucleoside class of
       antiretroviral agents does not contribute to the phenotypic and
       functional alterations related to P-glycoprotein during HIV infection.
 DE    Adult  Antiviral Agents/*PHARMACOLOGY  Cells, Cultured
       Didanosine/PHARMACOLOGY  Female  Human  HIV Seropositivity/*METABOLISM
       Immunophenotyping  Interleukin-2/PHARMACOLOGY  Lymphocyte Transformation
       Lymphocytes/DRUG EFFECTS/IMMUNOLOGY/*METABOLISM  Male
       P-Glycoprotein/*METABOLISM  Phytohemagglutinins/PHARMACOLOGY  Support,
       Non-U.S. Gov't  Zalcitabine/PHARMACOLOGY  Zidovudine/PHARMACOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

