CYP 3A proteins are expressed in human neutrophils and lymphocytes but are not induced by rifampicin

Life Sci. 1999;64(8):643-53. doi: 10.1016/s0024-3205(98)00606-7.

Abstract

Cytochrome P-450 3A (CYP 3A) enzymes, the prominent subfamily in the cytochrome system, are expressed in various extrahepatic tissues. Until now, their expression has been demonstrated in human polymorphic neutrophils (PMNs) but not in lymphocytes using immunohistochemistry and immunoblot analysis. Moreover, their potential modulation has not been determined yet. To study such an expression in different peripheral blood cell populations, rifampicin (600 mg/day during 6 days) was given to 8 healthy subjects. PMNs and lymphocytes were isolated by centrifugation of whole white blood cell fractions using Ficoll gradients before drug administration, immediately after, and 3 days after drug withdrawal. PMN and lymphocyte smears and homogenates were subjected to immunostaining and immunoblotting, respectively, with a mouse monoclonal antibody recognizing all CYP 3A proteins. These proteins were quantified by densitometric analysis. Before and after rifampicin administration, a positive cytoplasmic staining was observed in all PMNs and in about 50% of lymphocytes. CYP 3A expression in lymphocytes was further confirmed by positive immunoblots for lymphocyte homogenates. Neither in PMNs nor in lymphocytes, induction of CYP 3A protein expression was observed after rifampicin treatment despite overall induction of CYP 3A activity assessed by the urinary excretion of 6beta-hydroxycortisol. These results demonstrate that CYP 3A proteins are constitutively expressed not only in PMNs but also in lymphocytes. However, in both cell lineages CYP 3A protein expression was not induced by rifampicin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal
  • Aryl Hydrocarbon Hydroxylases*
  • Blotting, Western
  • Cell Separation
  • Cells, Cultured
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / immunology
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Enzyme Induction
  • Female
  • Humans
  • Hydrocortisone / analogs & derivatives
  • Hydrocortisone / urine
  • Immunohistochemistry
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism*
  • Male
  • Middle Aged
  • Molecular Weight
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Oxidoreductases, N-Demethylating / biosynthesis*
  • Oxidoreductases, N-Demethylating / immunology
  • Rifampin / administration & dosage
  • Rifampin / pharmacology*
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • 6 beta-hydroxycortisol
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating
  • Rifampin
  • Hydrocortisone