Differential expression of P-glycoprotein in cord blood and peripheral blood lymphocyte subpopulations

Abstract

P-glycoprotein (P-gP) is a 170 kDa glycoprotein encoded by MDR1 that appears to be involved in the secretion of a large number of molecules including hormones, cyclosporin A (CSA) and cytokines. Cord blood lymphocytes are functionally immature and are sensitive to CSA. Therefore, we compared the surface expression and function of P-gP in cord blood and peripheral blood CD4(+) and CD8(+) T cells and their naive (CD45RA(+)) and memory (CD45RO(+)) subsets. We observed that only 1% of cord blood CD4(+) and 2% CD8(+) cells expressed P-gP as compared to 7% and 10% respectively of peripheral blood from young controls. In addition, MDR1 mRNA levels were also decreased in cord blood mononuclear cells as compared to peripheral blood from young controls. The efflux function of P-gP was measured by intracellular accumulation of rhodamine 123 (Rh123, a substrate for P-gP) in the presence or absence of CSA. A higher accumulation of Rh123 was observed in cord blood CD4(+) and CD8(+) and their naive and memory cell subtype as compared to those in peripheral blood. Furthermore, cord blood CD4(+) and CD8(+) T cell subsets exhibited greater sensitivity towards CSA (% increase: 119 and 188 respectively) as compared to peripheral blood (44 and 89 respectively). A physiological role of decreased P-gP expression and function in cord blood remains to be determined.