Comparison of surfactant and perfluorochemical liquid enhanced adenovirus-mediated gene transfer in normal rat lung.
Both surfactant- and perfluorochemical (PFC)-based vehicles enhance adenovirus-mediated gene transfer in the lung. To compare the relative effects of surfactant and PFC liquid, we infected orotracheally intubated Sprague-Dawley rats with 4 x 10(9) pfu of an E1a(-)/E3(-) adenovirus expressing either an Escherichia coli lacZ (AdlacZ) mini-gene or no cDNA (Adnull). Surfactant-mediated delivery was achieved via instillation of four, 200-microl aliquots of virus suspended in a 50% surfactant (Survanta) vehicle over a 15-minute period. PFC rats received virus in 100 microl of saline followed by instillation of the PFC liquid FC-75 (10 cc/kg body weight) over a 2- to 3- minute period. Lungs were collected 3 days later for measurement of beta-galactosidase (beta-gal) expression and indices of inflammation. Both PFC liquid and surfactant-based vehicles produced widespread beta-gal expression and increased total beta-gal activity over that observed with instillation of vector alone. Both vehicles comparably increased bronchoalveolar lavage fluid (BALF), total cell counts, neutrophils, total protein, and IFN(gamma). FC-75 was also associated with increased BALF IL1beta. In conclusion, surfactant and FC-75 are similarly effective vehicles for adenovirus-mediated gene transfer to the lung.
Weiss
Daniel J
DJ
Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington 98105, USA. daniel.weiss@vtmednet.org
Mutlu
Gökhan M
GM
Bonneau
Laura
L
Mendez
Michael
M
Wang
Ying
Y
Dumasius
Vidas
V
Factor
Phillip
P
D000256:Adenoviridae / Q000378:metabolism*; D000818:Animals; D001688:Biological Products; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000187:drug effects; D005465:Fluorocarbon Polymers / Q000378:metabolism* / Q000494:pharmacology; D005466:Fluorocarbons; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019076:Transgenes
D001688:Biological Products; D016207:Cytokines; D005465:Fluorocarbon Polymers; D005466:Fluorocarbons; D011663:Pulmonary Surfactants; C429307:fluorocarbon 77; C072197:beractant