Relationship between adenovirus-mediated aquaporin 1 expression and fluid movement across epithelial cells.
AdhAQP1, a recombinant adenovirus encoding the human water channel aquaporin 1 (AQP1), has been shown to be useful for gene therapy of salivary glands rendered hypofunctional following irradiation. Here we utilized AdhAQP1 to examine the relationship between AQP1 expression and fluid movement across a polarized salivary epithelial cell monolayer. In response to a 440 to 340 mosm gradient, net fluid movement across cells infected with AdhAQP1 was approximately 10-fold that seen in uninfected cells or cells infected with a control virus. At a multiplicity of infection (MOI) of 5, fluid movement was linear for 15-30 min. Increasing the osmotic gradient resulted in a proportional increase in fluid movement. At low virus MOIs (0.1-1.0), fluid movement was markedly enhanced relative to that seen at higher MOIs (approximately 5.10), where the level of AQP1 expression and number of cells transduced were considerably greater. We conclude that significant, osmotically-obliged fluid movement in a salivary cell monolayer with low basal water permeability does not require high levels of AQP1 expression.
Delporte
C
C
Gene Therapy and Therapeutics Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hoque
A T
AT
Kulakusky
J A
JA
Braddon
V R
VR
Goldsmith
C M
CM
Wellner
R B
RB
Baum
B J
BJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins; D001692:Biological Transport; D001789:Blood Group Antigens; D002460:Cell Line; D016764:Cell Polarity; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005822:Genetic Vectors; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013363:Submandibular Gland / Q000166:cytology / Q000378:metabolism*; D014867:Water / Q000378:metabolism*
C496020:AQP1 protein, human; C496022:Aqp1 protein, rat; D020346:Aquaporins; D001789:Blood Group Antigens; D007473:Ion Channels; D011994:Recombinant Proteins; D014867:Water; D051398:Aquaporin 1