title: Role of plasminogen in propagation of scrapie.
abstract: To investigate whether plasminogen may feature in scrapie infection, we inoculated plasminogen-deficient (Plg(-/-)), heterozygous plasminogen-deficient (Plg(+/-)), and wild-type (Plg(+/+)) mice by the intracerebral or intraperitoneal (i.p.) route with the RML scrapie strain and monitored the onset of neurological signs of disease, survival time, brain, and accumulation of scrapie disease-associated forms of the prion protein (PrP(Sc)). Only after i.p. inoculation, a slight, although significant, difference in survival (P < 0.05) between Plg(-/-) and Plg(+/+) mice was observed. Neuropathological examination and Western blot analysis were carried out when the first signs of disease appeared in Plg(+/+) animals (175 days after i.p. inoculation) and when mice reached the terminal stage of illness. At the onset of symptoms, PrP(Sc) accumulation was higher in the brain and spleen of Plg(+/+) and Plg(+/-) mice than in those of Plg(-/-) mice, and these differences were paralleled by differences in the severity of spongiform changes and astrogliosis in the cerebral cortex and subcortical gray structures. Immunohistochemical analysis of the spleens before inoculation did not show any impairment of the immune system affecting follicular dendritic or lymphoid cells in Plg(-/-) mice. Once the disease progressed and mice began to die of infection, differences were no longer apparent in either brains or spleens. In conclusion, our data indicate that plasminogen has no major effect on the survival of scrapie agent-infected mice.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.forename: Raffaella
authors.initials: R
authors.lastname: Capobianco
authors.forename: Laura
authors.initials: L
authors.lastname: Colombo
authors.forename: Ada
authors.initials: A
authors.lastname: De Luigi
authors.forename: Giacomina
authors.initials: G
authors.lastname: Rossi
authors.forename: Michela
authors.initials: M
authors.lastname: Mangieri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.forename: Elena
authors.initials: E
authors.lastname: Quaglio
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiesa
authors.forename: Maria Benedetta
authors.initials: MB
authors.lastname: Donati
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D010958:Plasminogen / Q000235:genetics / Q000502:physiology*; D018620:PrPSc Proteins / Q000378:metabolism*; D012608:Scrapie / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
chemical_list: D018620:PrPSc Proteins; D010958:Plasminogen