NR ASVT
AU Mohan,J.; Hopkins,J.; Mabbott,N.A.
TI Skin-derived dendritic cells acquire and degrade the scrapie agent following in vitro exposure
QU Immunology 2005 Sep; 116(1): 122-33
PT journal article
AB The accumulation of the scrapie agent in lymphoid tissues following inoculation via the skin is critical for efficient neuroinvasion, but how the agent is initially transported from the skin to the draining lymph node is not known. Langerhans cells (LCs) are specialized antigen-presenting cells that continually sample their microenvironment within the epidermis and transport captured antigens to draining lymph nodes. We considered LCs probable candidates to acquire and transport the scrapie agent after inoculation via the skin. XS106 cells are dendritic cells (DCs) isolated from mouse epidermis with characteristics of mature LC cells. To investigate the potential interaction of LCs with the scrapie agent XS106 cells were exposed to the scrapie agent in vitro. We show that XS106 cells rapidly acquire the scrapie agent following in vitro exposure. In addition, XS106 cells partially degrade the scrapie agent following extended cultivation. These data suggest that LCs might acquire and degrade the scrapie agent after inoculation via the skin, but data from additional experiments demonstrate that this ability could be lost in the presence of lipopolysaccharide or other immunostimulatory molecules. Our studies also imply that LCs would not undergo maturation following uptake of the scrapie agent in the skin, as the expression of surface antigens associated with LC maturation were unaltered following exposure. In conclusion, although LCs or DCs have the potential to acquire the scrapie agent within the epidermis our data suggest it is unlikely that they become activated and stimulated to transport the agent to the draining lymph node.
IN
Langerhans-Zellen sind spezialisierte Antigen-präsentierende Zellen, die in der Haut Antigene "fressen", zerlegen und in Lymphknoten transportieren. Sie könnten deshalb auch durch die Haut eingedrungene Prionen ins Lymphsystem transportieren.
Die Autoren untersuchten diese Möglichkeit mit der dendritischen Zelllinie XS106, die ursprünglich aus Mausepidermis isoliert wurde und Eigenschaften reifer Langerhans-Zellen zeigt. Dazu gaben sie Scrapie-Infektiosität ins Medium dieser Zellen. Diese nahmen das PrPsc rasch auf und bauten es teilweise ab. Diese Fähigkeit wurde allerdings durch Lipopolysaccharide und andere immunstimulatorische Moleküle inhibiert. Die Autoren meinen, dass Langerhans-Zellen nach der Aufnahme von Prionen nicht mehr reifen und nicht mehr ins Lymphsystem wandern würden. Beweise haben sie für ihre beruhigende Hypothese aber offensichtlich nicht.
MH Animals; Antigens, Surface/analysis/metabolism; Brain/microbiology; Cell Differentiation; Cell Line; Gene Expression; Immunophenotyping; Langerhans Cells/*microbiology; Lipopolysaccharides/immunology; Mice; PrPc Proteins/biosynthesis/genetics; PrPsc Proteins/biosynthesis/genetics/*pathogenicity; Prion Diseases/immunology/metabolism/*microbiology; RNA, Messenger/genetics; Reverse Transcriptase Polymerase Chain Reaction/methods; Skin/*microbiology
AD Institute for Animal Health, Edinburgh, UK
SP englisch
PO England