epidermal-growth-factor and Orthomyxoviridae-Infections

Morphological signs of early interstitial fibrosis, developing under conditions of acute viral inflammation (postinfection days 1-14), were observed in C57Bl/6 mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus. The development of fibrosis was confirmed by an increase in the number of lung cells expressing TNF-α. These changes were recorded in the presence of a many-fold increase in the counts of macrophages and fibroblasts expressing FGF, EGF, and their receptors.

Topics: Animals; Epidermal Growth Factor; ErbB Receptors; Fibroblast Growth Factors; Fibroblasts; Histological Techniques; Immunohistochemistry; Influenza A Virus, H5N1 Subtype; Macrophages, Alveolar; Male; Mice; Mice, Inbred C57BL; Orthomyxoviridae Infections; Pulmonary Fibrosis; Receptors, Fibroblast Growth Factor

Gene transfer to skin has many potential applications but lacks a safe, practical delivery method. This report presents a new technique, microseeding, for in vivo gene transfer to skin and wounds and for DNA-mediated vaccination. The plasmid DNA solution was delivered directly to the target cells of the skin by a set of oscillating solid microneedles driven by a modified tattooing device.. Skin and partial-thickness excisional wounds in pigs were microseeded with either hEGF expression plasmid or beta-galactosidase expression plasmid. Human EGF was also delivered by single injection or particle bombardment. hEGF expression in wound fluid and in target tissue was determined by ELISA with anti-hEGF-specific antibodies. Additionally, weanling pigs were microseeded with a hemagglutinin of swine influenza virus expression plasmid and production of anti-HA-specific antibodies was determined by blocking ELISA.. hEGF expression in microseeded partial thickness wounds (5664 pg/site) and skin sites (969 pg/site) peaked 2 days after transfection being four- to seven-fold higher than gene transfer by a single intradermal injection and two- to three-fold higher than particle-mediated gene transfer. The beta-galactosidase-expressing cells were detected in dermis and epidermis. Pigs microseeded with HA expression plasmid were protected from infection by the Swine influenza virus.. These results demonstrate that microseeding is a simple and effective method for in vivo gene transfer to skin and wounds and is more efficient than single injection and particle-mediated gene transfer.

Topics: Animals; beta-Galactosidase; Epidermal Growth Factor; Female; Gene Expression Regulation, Enzymologic; Gene Transfer Techniques; Histocompatibility Antigens; Influenza A virus; Orthomyxoviridae Infections; Plasmids; Skin Physiological Phenomena; Swine; Tattooing; Vaccination; Wound Healing