MDR1-Pgp 170 expression in human bronchus.
MDR1 P-glycoprotein (Pgp 170), a member of the adenosine triphosphate (ATP) binding cassette transporters, acts as an efflux pump for various hydrophobic agents, particularly for xenobiotics such as benzo(a)pyrene. It has also been shown to regulate cell-volume activated chloride channels. Pgp 170 could, therefore, be of particular importance in cellular mechanisms of defence in the airways and in the control of mucus layer composition. For these reasons, we evaluated the precise localization of Pgp 170 in human adult airways. Fresh non-neoplastic bronchial specimens were collected from 33 patients (26 smokers, four exsmokers and three nonsmokers) who underwent surgery for lung carcinoma. The presence of MDR1 messenger ribonucleic acid (mRNA) was demonstrated by reverse transcriptase chain reaction (RT-PCR) in bronchial epithelial cells collected by gentle scraping from either smokers, exsmokers or nonsmokers. Immunodetection of Pgp 170 using a panel of monoclonal antibodies (MRK16, JSB1, C219, C494) was performed either on cryostat or paraffin-embedded sections of histologically normal bronchial tissue. Pgp 170 was constantly detected with intense labelling at the apical surface of ciliated epithelial cells from the surface epithelium or ciliated collecting ducts, and on apical and lateral surfaces of serous cells from bronchial glands. No staining of mucus-secreting cells was observed. Pgp 170 was also demonstrated at the luminal surface of endothelial cells of bronchial capillaries. In conclusion, the expression of MDR1 P-glycoprotein in bronchial structures, particularly at the epithelial apical surface, suggests important roles for this transmembrane protein in human airways.
Lechapt-Zalcman
E
E
Histology and Tumour-Biology Laboratory, Hôpital Tenon, Paris, France.
Hurbain
I
I
Lacave
R
R
Commo
F
F
Urban
T
T
Antoine
M
M
Milleron
B
B
Bernaudin
J F
JF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001980:Bronchi / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger