Involvement of P-gp in the process of apoptosis in peripheral blood mononuclear cells

Int Immunopharmacol. 2005 May;5(5):821-8. doi: 10.1016/j.intimp.2004.12.014. Epub 2005 Jan 21.

Abstract

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / immunology
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • Adult
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cortisone / pharmacology
  • Dexamethasone / pharmacology
  • Female
  • Humans
  • In Vitro Techniques
  • Leukocytes, Mononuclear / cytology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Male
  • Methotrexate / pharmacology
  • Methylprednisolone / pharmacology
  • Middle Aged
  • Phytohemagglutinins / pharmacology
  • Verapamil / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibodies, Monoclonal
  • Phytohemagglutinins
  • Dexamethasone
  • Verapamil
  • Cortisone
  • Methylprednisolone
  • Methotrexate