scholarly journals Expression of multidrug resistance P-glycoprotein on peripheral blood mononuclear cells of patients with granular lymphocyte-proliferative disorders

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1342-1346
Author(s):  
T Yamamoto ◽  
T Iwasaki ◽  
N Watanabe ◽  
K Oshimi ◽  
M Naito ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Killer Cell ◽  
Chemotherapeutic Agents ◽  
Cell Type ◽  
Peripheral Blood Mononuclear ◽  
P Glycoprotein ◽  
Blood Mononuclear Cells

Some patients with granular lymphocyte-proliferative disorders (GLPD) have been reported to have an aggressive clinical course with a poor prognosis and to be refractory to chemotherapy. In this study, expression of multidrug resistance P-glycoprotein on peripheral blood mononuclear cells (PBMC) of 11 patients with GLPD was examined by staining with MRK 16, a monoclonal antibody that binds to an external epitope of P-glycoprotein, and with the dye rhodamine, a known substance to be excreted from the cells through P-glycoprotein. Among those tested, the PBMC of six of eight patients with T-cell-type GLPD as well as those of three of three patients with natural killer cell- type GLPD expressed P-glycoprotein significantly. Furthermore, PBMC of two of two patients were also poorly stained with the dye rhodamine, and the treatment of PBMC with either verapamil or quinidine, multidrug resistance-reversing agents, led to their increased staining, suggesting that these PBMC actively release chemotherapeutic agents.

scholarly journals Expression of multidrug resistance P-glycoprotein on peripheral blood mononuclear cells of patients with granular lymphocyte-proliferative disorders

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1342-1346 ◽  
Author(s):  
T Yamamoto ◽  
T Iwasaki ◽  
N Watanabe ◽  
K Oshimi ◽  
M Naito ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Killer Cell ◽  
Chemotherapeutic Agents ◽  
Cell Type ◽  
Peripheral Blood Mononuclear ◽  
P Glycoprotein ◽  
Blood Mononuclear Cells

Abstract Some patients with granular lymphocyte-proliferative disorders (GLPD) have been reported to have an aggressive clinical course with a poor prognosis and to be refractory to chemotherapy. In this study, expression of multidrug resistance P-glycoprotein on peripheral blood mononuclear cells (PBMC) of 11 patients with GLPD was examined by staining with MRK 16, a monoclonal antibody that binds to an external epitope of P-glycoprotein, and with the dye rhodamine, a known substance to be excreted from the cells through P-glycoprotein. Among those tested, the PBMC of six of eight patients with T-cell-type GLPD as well as those of three of three patients with natural killer cell- type GLPD expressed P-glycoprotein significantly. Furthermore, PBMC of two of two patients were also poorly stained with the dye rhodamine, and the treatment of PBMC with either verapamil or quinidine, multidrug resistance-reversing agents, led to their increased staining, suggesting that these PBMC actively release chemotherapeutic agents.

scholarly journals Peripheral blood mononuclear cells preferentially activate 11-oxygenated androgens

2020 ◽  
Author(s):  
Lina Schiffer ◽  
Alicia Bossey ◽  
Angela E Taylor ◽  
Ildem Akerman ◽  
Dagmar Scheel-Toellner ◽  
...  
Keyword(s):  
Natural Killer ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Killer Cell ◽  
Blood Collection ◽  
Target Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

AbstractContextAndrogens are important modulators of immune cell function impacting proliferation, differentiation and cytokine production. The local generation of active androgens from circulating androgen precursors is an important mediator of androgen action in peripheral androgen target cells or tissue.ObjectiveTo characterize the activation of classic and 11-oxygenated androgens in human peripheral blood mononuclear cells (PBMCs).MethodsPBMCs were isolated from healthy male donors and incubated ex vivo with precursors and active androgens of the classic and 11-oxygenated androgen pathways. Steroids were quantified by liquid chromatography-tandem mass spectrometry. The expression of genes encoding steroid-metabolizing enzymes was assessed by quantitative PCR.ResultsPBMCs generated 8-fold higher amounts of the active 11-oxygenated androgen 11-ketotestosterone than the classic androgen testosterone from their respective precursors. We identified the enzyme AKR1C3 as the major reductive 17β-hydroxysteroid dehydrogenase in PBMCs responsible for both conversions and found that within the PBMC compartment natural killer cells are the major site of AKRC13 expression and activity. Steroid 5α-reductase type 1 catalyzed the 5α-reduction of classic but not 11-oxygenated androgens in PBMCs. Lag time prior to the separation of cellular components from whole blood increased 11KT serum concentrations in a time-dependent fashion, with significant increases detected from two hours after blood collection.Conclusions11-oxygenated androgens are the preferred substrates for androgen activation by AKR1C3 in PBMCs, primarily conveyed by natural killer cell AKR1C3 activity, yielding 11KT the major active androgen in PBMCs. Androgen metabolism by PBMCs can affect the measurement results of serum 11-ketotestosterone concentrations, if samples are not separated in a timely fashion.

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