RELATIONSHIP BETWEEN ADENOVIRUS-MEDIATED AQUAPORIN EXPRESSION AND FLUID MOVEMENT ACROSS EPITHELIAL-CELLS

AdhAQP1, a recombinant adenovirus encoding the human water channel aqu aporin 1 (AQP1), has been shown to be useful for gene therapy of saliv ary glands rendered hypofunctional following irradiation. Here we util ized AdhAQP1 to examine the relationship between AQP1 expression and f luid movement across a polarized salivary epithelial cell monolayer. I n response to a 440 to 340 mosm gradient, net fluid movement across ce lls infected with AdhAQP1 was similar to 10-fold that seen in uninfect ed cells or cells infected with a control virus. At a multiplicity of infection (MOI) of 5, fluid movement was linear for 15-30 min. Increas ing the osmotic gradient resulted in a proportional increase in fluid movement. At low virus MOIs (0.1-1.0), fluid movement was markedly enh anced relative to that seen at higher MOIs (similar to 5-10), where th e level of AQP1 expression and number of cells transduced were conside rably greater. We conclude that significant, osmotically-obliged fluid movement in a salivary cell monolayer with low basal water permeabili ty does not require high levels of AQP1 expression. (C) 1998 Academic Press.