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Gene
Therapy and Therapeutics Branch (CD, BJB), National Institute of Dental
Research, National Institutes of Health, Bethesda, Maryland; and Oral Pathology
Research Laboratory (RSR), Department of Veterans Affairs Medical Center,
Washington, D.C. |
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This study compared the
localization of the alpha vbeta 3/5 integrins in the different cell types
of the rat submandibular gland with the susceptibility of these cells to
infection by an intraductally administered replication-deficient recombinant
type 5 adenovirus coding for rat aquaporin 5 (termed AdrAQP5). We used a
panel of antibodies and immunohistochemical procedures to determine the
luminal membrane distribution of the integrins. The alpha vbeta 3/5 integrin
subunits were present in luminal membranes of all ductal cell types and
acini; however, the alphav subunit was found to a lesser extent in the acini.
After AdrAQP5 infection, the expression of AQP5 exhibited a similar, though
not identical, cellular localization to that seen for alpha vbeta 3/5 integrins.
AdrAQP5 infected all cell types in these glands, except excretory ducts,
after intraductal administration, directing the transient expression of
AQP5. In addition, the localization of alpha vbeta 3/5 integrins was examined
in rabbit, monkey, and human submandibular and parotid glands. Although
there were some interspecies differences, glands generally displayed the
presence of these integrin subunits on luminal membranes of ductal cells
and most acinar cells. These findings show that the presence of alpha vbeta
3/5 integrins on the luminal membranes of rat salivary epithelial cells
is associated with the susceptibility of these cells to act as targets for
adenoviral-mediated gene transfer. However, the abundance of alpha vbeta
3/5 integrin expression was not necessarily predictive of the extent of
transgene expression in a particular cell type. Furthermore, because the
salivary glands of rabbits, monkeys, and humans show a similar luminal membrane
distribution of these integrins, it is likely that recombinant type 5 adenoviruses
may be able to mediate in vivo gene transfer to salivary glands in these
species. |
