CYP 3A proteins are expressed in human neutrophils and lymphocytes but arenot induced by rifampicin

Cytochrome P-450 3A (CYP 3A) enzymes, the prominent subfamily in the cytoch rome system, are expressed in various extrahepatic tissues. Until now, thei r 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, rifampic in (600 mg/day during 6 days) was given to 8 healthy subjects. PMNs and lym phocytes were isolated by centrifugation of whole white blood cell fraction s using Ficoll gradients before drug administration, immediately after, and 3 days after drug withdrawal. PMN and lymphocyte smears and homogenates we re subjected to immunostaining and immunoblotting, respectively, with a mou se monoclonal antibody recognizing all CYP 3A proteins. These proteins were quantified by densitometric analysis. Before and after rifampicin administ ration, a positive cytoplasmic staining was observed in all PMNs and in abo ut 50% of lymphocytes. CYP 3A expression in lymphocytes was further confirm ed by positive immunoblots for lymphocyte homogenates. Neither in PMNs nor in lymphocytes, induction of CYP 3A protein expression was observed after r ifampicin treatment despite overall induction of CYP 3A activity assessed b y the urinary excretion of 6 beta-hydroxycortisol. These results demonstrat e that CYP 3A proteins are constitutively expressed not only in PMNs but al so in lymphocytes. However, in both cell lineages CYP 3A protein expression was not induced by rifampicin.