Multidrug resistance-1 (MDR-1) in autoimmune disorders III: increased P-glycoprotein activity in lymphocytes from immune thrombocytopenic purpura patients.
Exp Hematol
; 31(6): 483-7, 2003 Jun.
Article
em En
| MEDLINE
| ID: mdl-12829023
ABSTRACT
OBJECTIVE:
P-glycoprotein (P-gp) expression has been widely observed in normal and neoplastic cells. The physiologic role of P-gp involves hormone and metabolite secretion, bacterial product detoxification, and transport of several drugs to the extracellular space. Multidrug resistance-1 is characterized by drug extrusion through P-gp, reducing the intracellular levels of drugs and diminishing their pharmacological effects. Treatment of immune thrombocytopenic purpura (ITP) includes agents that are substrates of P-gp; hence, the objective of this study was to analyze the functional activity of P-gp in lymphocytes from patients with ITP. PATIENTS ANDMETHODS:
30 ITP patients (9 refractory, 5 dependent, 14 responders to treatment, and 2 with stable disease) and 25 healthy controls were studied. Peripheral blood mononuclear cells were isolated by gradient centrifugation and incubated with daunorubicin (a fluorescent drug extruded by P-gp). Functional activity of P-gp was analyzed by flow cytometry. Results were expressed as the percentage of lymphocytes able to extrude daunorubicin.RESULTS:
ITP patients showed an increased number of lymphocytes with P-gp activity (mean=12.3%+/-16%) when compared to controls (mean=0.87%+/-0.72%) (p<0.05). P-gp function was higher in the refractory group (median=9.4%) than in the treatment-dependent (median=5.4%), responder (median=6.4%), and stable disease (median=5.2%) groups, although no statistical differences were found among them.CONCLUSION:
Enhanced P-gp activity in ITP may be related to an unfavorable clinical outcome and poor response to treatment. Furthermore, P-gp function might affect therapeutic requirements for disease control.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos
/
Púrpura Trombocitopênica Idiopática
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article