Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1994-6-1
pubmed:abstractText
In contrast to its clearly defined role as a multidrug efflux pump in neoplastic cells, the physiologic function of P-glycoprotein (P-gly) in normal cells is unclear. Recent reports identifying P-gly in normal blood and bone marrow suggest that hematopoietic development or function may be dependent on P-gly. To understand the normal function of P-gly in the blood, its level of expression and function must first be quantitated relative to a known standard. In this study, P-gly, MDR1 gene expression, and P-gly function were quantitated in normal leukocytes. P-gly and MDR1 expression were analyzed in individual leukocyte lineages (T-helper, T-suppressor, monocyte, granulocyte, B-lymphocyte, NK cell) from normal volunteers. P-gly on the cell surface was detected by fluorescent double-labeling for lineage (CD4, CD8, CD14, CD15, CD19, CD56, respectively) and P-gly (MRK16) with analysis by flow cytometry and in some cases immunoblot analysis. MDR1 mRNA analysis on purified lineages was performed using quantitative reverse transcription-polymerase chain reaction. P-gly function was determined for each lineage using dual-labeling for lineage and P-gly substrate (rhodamine 123). The P-gly expressing human myeloma cell line, 8226/Dox6, was used as a reference of comparison for levels of P-gly, MDR1 mRNA, and function. CD56+ cells expressed the highest levels of MDR1 mRNA followed by CD8+ > CD4+ approximately equal to CD15+ > CD19+ > CD14+, with percentage values relative to Dox6 of 49%, 17%, 8%, 8%, 4%, and 2%, respectively. The assays for P-gly immunofluorescence and function correlated well with mRNA analysis except for CD15+ cells (granulocytes), which showed a moderate MDR1 mRNA level with a lack of both function and surface P-gly staining. Granulocyte membranes did show P-gly on immunoblot analysis when probed with either C219 or JSB1. We conclude that (1) P-gly and the MDR1 mRNA are expressed in normal leukocytes, (2) this P-gly expression is lineage specific with relatively high levels among CD56+ cells, and (3) the expression of P-gly in granulocytes is not associated with transport of the P-gly substrate, rhodamine 123, out of the cell.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2451-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7513198-Antigens, CD, pubmed-meshheading:7513198-B-Lymphocytes, pubmed-meshheading:7513198-Carrier Proteins, pubmed-meshheading:7513198-Drug Resistance, pubmed-meshheading:7513198-Flow Cytometry, pubmed-meshheading:7513198-Fluorescent Antibody Technique, pubmed-meshheading:7513198-Gene Expression, pubmed-meshheading:7513198-Granulocytes, pubmed-meshheading:7513198-Humans, pubmed-meshheading:7513198-Immunoblotting, pubmed-meshheading:7513198-Killer Cells, Natural, pubmed-meshheading:7513198-Leukocytes, pubmed-meshheading:7513198-Membrane Glycoproteins, pubmed-meshheading:7513198-Monocytes, pubmed-meshheading:7513198-P-Glycoprotein, pubmed-meshheading:7513198-Polymerase Chain Reaction, pubmed-meshheading:7513198-RNA, pubmed-meshheading:7513198-RNA, Messenger, pubmed-meshheading:7513198-T-Lymphocytes, Helper-Inducer, pubmed-meshheading:7513198-T-Lymphocytes, Regulatory
pubmed:year
1994
pubmed:articleTitle
P-glycoprotein expression and function in circulating blood cells from normal volunteers.
pubmed:affiliation
Arizona Cancer Center, University of Arizona, Tucson 85724.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.