Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part II: Increased P-glycoprotein activity in lymphocytes from systemic lupus erythematosus patients might affect steroid requirements for disease control.
BACKGROUND
Over-expression of the membrane glycoprotein called P-glycoprotein has been widely observed in a variety of both normal and neoplastic cells. P-glycoprotein is a pump molecule that transports hydrophobic drugs (including steroids) and toxins outside the cells, thus inhibiting their therapeutic or toxic effects. The gene encoding P-glycoprotein is named multidrug resistance-1 (MDR-1).


OBJECTIVE
To evaluate the functional activity of P-glycoprotein in lymphocytes and monocytes from patients with systemic lupus erythematosus.


METHODS
30 systemic lupus erythematosus patients and 20 healthy controls were studied. Peripheral blood mononuclear cells isolated by gradient centrifugation were incubated in the presence of daunorubicin (a fluorescent drug extruded by P-glycoprotein) at 37 degrees C or 4 degrees C for 30 min. P-glycoprotein activity was then analyzed using flow cytometry. Results were expressed as the percentage of lymphocytes or monocytes with high P-glycoprotein activity (i.e., low fluorescence).


RESULTS
Mean fluorescence values for lymphocytes and monocytes were comparable between patients and healthy controls. However, because our method allowed to measure P-glycoprotein function at the single-cell level, we were able to show that the mean percentage of lymphocytes with high P-glycoprotein activity was increased in the patients (11.51% +/- 14.3%) as compared to the healthy controls (0.71% +/- 0.57%) (P < 0.05). Moreover, P-glycoprotein activity was lower in the patients in clinical remission than in those with active disease.


CONCLUSIONS
Our results suggest that P-glycoprotein function might affect glucocorticoid requirements in systemic lupus erythematosus.
Diaz-Borjon
A
A
Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico.
Richaud-Patin
Y
Y
Alvarado de la Barrera
C
C
Jakez-Ocampo
J
J
Ruiz-Argüelles
A
A
Llorente
L
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002452:Cell Count; D003630:Daunorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D019450:Genes, MDR; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011241:Prednisone / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014700:Verapamil / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014700:Verapamil; D011241:Prednisone; D003630:Daunorubicin