Anti-LRP/LR antibody W3 hampers peripheral PrPSc propagation in scrapie infected mice.
We identified the 37kDa/67kDa laminin receptor (LRP/LR) as a cell surface receptor for the cellular prion protein (PrP(c)) and the infectious prion protein (PrP(Sc)). Recently, we showed that anti-LRP/LR antibody W3 cured scrapie infected N2a cells. Here, we demonstrate that W3 delivered by passive immunotransfer into C57BL/6 mice reduced the PrP(Sc) content in the spleen significantly by 66%, demonstrating an impairment of the peripheral PrP(Sc) propagation. In addition, we observed a 1.8-fold increase in survival of anti-LRP/LR antibody W3 treated mice (mean survival of 31 days) compared to preimmune serum treated control animals (mean survival of 17 days). We conclude that the significant effect of anti-LRP/LR antibody W3 on the reduction of peripheral PrP(Sc) propagation might be due to the blockage of the prion receptor LRP/LR which is required, as previously shown in vitro, for PrP(Sc) propagation in vivo.
Zuber
Chantal
C
Laboratorium für Molekulare Biologie-Genzentrum, Institut für Biochemie der Ludwig-Maximilians-Universitat München, München, Germany.
Mitteregger
Gerda
G
Pace
Claudia
C
Zerr
Inga
I
Kretzschmar
Hans A
HA
Weiss
Stefan
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D007116:Immunization, Passive; D051379:Mice; D018620:PrPSc Proteins / Q000276:immunology*; D017474:Receptors, Laminin / Q000037:antagonists & inhibitors* / Q000276:immunology; D012608:Scrapie / Q000188:drug therapy* / Q000276:immunology; D012756:Sheep; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D018620:PrPSc Proteins; D017474:Receptors, Laminin