Neonatal murine epidermal cells express a functional multidrug-resistant pump

Phospho-glycoproteins are members of the ABC transporter family encoded by the multidrug-resistant genes. These proteins are highly expressed in many tumor cells derived from patients undergoing treatment with anti-cancer dru gs. Phospho-glycoproteins are large 12 transmembrane spanning molecules of 170 kDa, involved in adenosine-5'-triphosphate-dependent efflux of molecule s out of the cell, known currently as multidrug-resistant pumps. Expression analysis of phospho-glycoproteins in mice and humans indicates widespread distribution in a number of organs, such as brain and testis. We have analy zed skin, and more particularly keratinocytes, to determine whether they ex press phospho-glycoproteins and express the multidrug-resistant phenotype. Immunofluorescent staining of skin showed that keratinocytes located in the basal layer of the epidermis preferentially expressed phospho-glycoprotein s, as did the outer root sheath cells of hair follicles. Phospho-glycoprote in expression on the basal cells was restricted to the cell surface. Polyme rase chain reaction analysis of first strand cDNA from keratinocytes identi fied the phospho-glycoproteins to be mdr1b. Using beta 1 integrin expressio n and density gradient centrifugation we were able to enrich and identify t he basal cell compartment by flow cytometric analysis and assay this subset of cells for phospho-glycoprotein activity. Basal cells loaded with rhodam ine 123, a substrate for multidrug-resistant pumps, effluxed the molecule f rom the cells in a time-dependent manner. This study shows that basal layer keratinocytes express functional phospho-glycoproteins. We speculate that phospho-glycoproteins may play a role in regulating the level of environmen tal toxins and differentiation factors, as has been suggested for other pro genitor cell compartments.