Involvement of P-gp in the process of apoptosis in peripheral blood mononuclear cells.
Multidrug resistance mediated by the drug-efflux protein P (P-gp) is one of mechanisms that cells use to escape death induced by drugs and other agents. The aim of the study was to evaluate the effect of P-gp inhibition on apoptosis of PHA-activated peripheral blood mononuclear cells (MNC) as well as apoptosis induced by methotrexate (MTX), dexamethasone (DEX), methylprednisolone (MP) and cortisone (COR). Apoptosis was quantified by flow cytometry using Annexin V/PI and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL). P-gp expression was inhibited using verapamil (VER) and P-gp specific monoclonal antibodies (mAb). VER and mAb enhanced the apoptosis of PHA-activated MNC. Moreover these agents significantly increased the apoptosis induced by MTX, DEX, MP and COR. The results of this study suggest that P-gp is involved in the process of apoptosis in peripheral blood mononuclear cells.
Pawlik
A
A
Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, 70-111 Szczecin, al. Powstañców Wlkp. 72, Poland. pawand@poczta.onet.pl
Baskiewicz-Masiuk
M
M
Machalinski
B
B
Gawronska-Szklarz
B
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D003348:Cortisone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D008775:Methylprednisolone / Q000494:pharmacology; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D010835:Phytohemagglutinins; D003907:Dexamethasone; D014700:Verapamil; D003348:Cortisone; D008775:Methylprednisolone; D008727:Methotrexate