title: The effect of gene gun-delivered pGM-CSF on the immunopathology of the vaccinated skin.
abstract: The aim of this study was to investigate the skin immunopathology of gene gun-delivered plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) and hence explore the possible mechanisms of its adjuvant activity. Using sheep as the experimental model, expressible pGM-CSF was administered to the epidermis and the dermal/epidermal junction and its effects on the skin were assessed by histopathology, immunohistology and quantitative RT-PCR for a range of pro-inflammatory and immune response-polarizing cytokines. Both functional and non-functional plasmids caused an acute inflammatory response with the infiltration of neutrophils and micro-abscess formation; however, the response to pGM-CSF was more severe and was also associated with the accumulation of eosinophils, immature (CD1b(-)/CD172a(-)) dendritic cells and B cells. In terms of cytokine expression, an early TNF-alpha response was stimulated by gene gun delivery of plasmid-associated gold beads, which coincided with an immediate infiltration of neutrophils. However, only pGM-CSF triggered the short-lived expression of GM-CSF (peaking at 4 h) and significant long-term increases in both TNF-alpha and IL-1beta. pGM-CSF did not affect the expression of the immune response-polarizing cytokines, IL-10 and IL-12.
authors.affiliation: Centre of Infectious Diseases, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall, Edinburgh, UK.
authors.forename: K
authors.initials: K
authors.lastname: Matthews
authors.forename: S M
authors.initials: SM
authors.lastname: Rhind
authors.forename: A G
authors.initials: AG
authors.lastname: Gossner
authors.forename: R G
authors.initials: RG
authors.lastname: Dalziel
authors.forename: J
authors.initials: J
authors.lastname: Hopkins
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D019470:Biolistics; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D007150:Immunohistochemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D012867:Skin / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor