Vascular cell adhesion molecule-1 augments adenovirus-mediated gene transfer

We have reported that adenovirus-mediated gene transfer is augmented in the endothelium of atherosclerotic blood vessels. We observed that vascular ce ll adhesion molecule-1 (VCAM-1) shares some homology with the coxsackieviru s and adenovirus receptor. Because VCAM-1 is upregulated on atherosclerotic endothelial cells, we hypothesized that VCAM-1 may act as an auxiliary rec eptor to augment adenovirus-mediated gene transfer. To test this hypothesis , stable NIH 3T3 cell lines that constitutively express VCAM-1 on the cell surface were generated. Recombinant adenovirus 5 (Ad5), which contains the reporter beta -galactosidase gene, was used to compare Ad5 infection in VCA M-1(+) and parental NIH 3T3 cells. Total beta -galactosidase activity and t he number of transgene-positive cells were 6- to 10-fold and 5-fold higher, respectively, in VCAM-1(+) than in VCAM-1(-) cells. Ad5 binding to VCAM-1( +) cells was increased by 3-fold over VCAM-1(-) cells. Soluble VCAM-1 prote in, present during infection or viral binding, reduced P-galactosidase acti vity in VCAM-1(+) cells in a dose-dependent manner. Taken together, we conc lude that VCAM-1 can mediate adenovirus binding and infection. This may exp lain, in part, the previous finding that adenovirus-mediated gene transfer is augmented in atherosclerotic arteries.