Recombinant E1-deleted adenoviral vectors induce apoptosis in a rat airway epithelial mucous goblet cell line.
Replication-defective adenoviruses (Ad) are used as vectors for delivering therapeutic genes to human airway cells. We examined whether E1-deleted Ad vectors (Ad5-CMV-LacZ) had effects on cell kinetics in SPOC1 cells, which is a rat airway epithelial mucous goblet cell line. There was a vector multiplicity of infection (moi)-dependent increase of the transduction efficiency of the LacZ reporter gene in SPOC cells. Cell proliferation was inhibited in the vector-infected cells compared with that in vehicle-exposed cells. However, increased cell death was observed in the vector-infected cells with a higher moi. The morphology of vector-exposed cells revealed apoptotic features including nuclear condensation and a fragmented nucleus. These results indicate that higher moi of vectors allows the cells to achieve higher gene transfer, but also induce apoptosis of infected cells. Minimizing the induction of apoptosis of vector-infected cells may be an important strategy for the prolongation of transduction efficiency of Ad vectors in airway epithelial mucous goblet cells.
Teramoto
S
S
Department of Geriatric Medicine, Tokyo University Hospital, Japan.
Matsuse
T
T
Matsui
H
H
Ohga
E
E
Ishii
T
T
Nagase
T
T
Ouchi
Y
Y
D000256:Adenoviridae / Q000235:genetics*; D017498:Adenovirus E1 Proteins / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D017353:Gene Deletion; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics* / Q000494:pharmacology; D020397:Goblet Cells / Q000166:cytology*; D007763:Lac Operon; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000494:pharmacology; D014161:Transduction, Genetic
D017498:Adenovirus E1 Proteins; D011993:Recombinant Fusion Proteins