P-glycoprotein expression in circulating blood leukocytes of patients with steroid-resistant asthma

P-Glycoprotein is a transmembrane efflux pump for different lipophilic drugs including glucocorticosteroids. Thus, upregulation of P-glycoprotein may provide a mechanism for reduced glucocorticosteroid responses as they occur in steroid-resistant asthma. To address this issue, we have examined freshly isolated peripheral blood mononuclear cells and granulocytes with regards to P-glycoprotein functional and surface expression. Using two-color immuno fluorescence techniques, we demonstrated a direct correlation between the efflux of the fluorescent dye Rh 123 and P-glycoprotein surface expression in lymphocytes, NK (natural killer) cells, monocytes and granulocytes. P-Glycoprotein levels varied widely between different leucocytes, with NK cells and CD8+ T cells having high, and granulocytes having no detectable levels. There was no evidence for upregulation of P-glycoprotein expression in any cell type from patients with steroid-resistant asthma compared to patients with steroid-sensitive or mild asthma. These results suggest that increased P-glycoprotein expression can be excluded as a mechanism for steroid resistance. Interestingly, a down regulation of P-glycoprotein expression in B cells was associated with systemic glucocorticosteroid treatment in vivo and in vitro. Whether this phenomenon may account for reduced immunoglobulin levels associated with oral glucocortico-steroid therapy remains to be determined.