Prion cell tropism varies significantly among animal species, depending on both the agent strain and host-specific factors. For example, prions show high lymphotropism in scrapie infected sheep and vCJD, but little, if any, in sporadic CJD or BSE. In particular, the BSE strain is associated with significant PrP-res accumulation in tonsils, spleen and appendix in humans, whereas, it is largely confined to the CNS in infected cattle. Given that cellular prion protein (PrPC), is sine qua non for PrP-res formation and the development of TSE, it is well possible that tissue-specific PrPC properties may represent one of the host factors influencing the cell tropism of the infectious agent. We applied a western blot analyses to compare the relative percentage of the di-, mono- and unglycosylated PrPC (i.e. glycoform ratio) as well as the expression of truncated PrPC forms in tissues from the CNS and lymphoid structures (lymphoid follicles, lymphocytes and follicular dendritic cells) of bovine and human. We found that PrPC glycoform ratio is significantly different between cerebellum and medulla in both species. Moreover, the expression of truncated PrPC (i.e. 21 and 18 kDa fragments) was significantly heterogenous according to the brain region investigated. PrPC was highly glycosylated in spleen and lymphoid follicles isolated from bovine tonsils, mesenteric lymph nodes, ileal and jejunal Peyer’s patches. After deglycosylation, a novel PrPC truncated form with a relative molecular mass of about 25 kDa was detected in bovine lymphoid organs beside the 18 and 21 kDa forms. No difference in PrPC profile was seen in human lymphocytes extracted either from spleen or tonsil. Our results highlight variations in the tissue expression profile of PrPC in bovine and human. Such differences may have an implication for PrPC function or may represent critical factors influencing the accumulation of the infectious agent in different tissues.
Characterization of bovine and human cellular prion protein expressed in the central nervous system and in lymphoid organs / V. Defaweux; R. Strammiello; S. Capellari; N. Antoine; C. Demonceau; G. Dorban; O. Jolois; E. Heinen; P. Parchi. - STAMPA. - 1:(2005), pp. 304-304. (Intervento presentato al convegno Prion 2005. Between fundamentals and society's needs tenutosi a Dusseldorf nel 19-21 ottobre 2005).
Characterization of bovine and human cellular prion protein expressed in the central nervous system and in lymphoid organs
CAPELLARI, SABINA;PARCHI, PIERO
2005
Abstract
Prion cell tropism varies significantly among animal species, depending on both the agent strain and host-specific factors. For example, prions show high lymphotropism in scrapie infected sheep and vCJD, but little, if any, in sporadic CJD or BSE. In particular, the BSE strain is associated with significant PrP-res accumulation in tonsils, spleen and appendix in humans, whereas, it is largely confined to the CNS in infected cattle. Given that cellular prion protein (PrPC), is sine qua non for PrP-res formation and the development of TSE, it is well possible that tissue-specific PrPC properties may represent one of the host factors influencing the cell tropism of the infectious agent. We applied a western blot analyses to compare the relative percentage of the di-, mono- and unglycosylated PrPC (i.e. glycoform ratio) as well as the expression of truncated PrPC forms in tissues from the CNS and lymphoid structures (lymphoid follicles, lymphocytes and follicular dendritic cells) of bovine and human. We found that PrPC glycoform ratio is significantly different between cerebellum and medulla in both species. Moreover, the expression of truncated PrPC (i.e. 21 and 18 kDa fragments) was significantly heterogenous according to the brain region investigated. PrPC was highly glycosylated in spleen and lymphoid follicles isolated from bovine tonsils, mesenteric lymph nodes, ileal and jejunal Peyer’s patches. After deglycosylation, a novel PrPC truncated form with a relative molecular mass of about 25 kDa was detected in bovine lymphoid organs beside the 18 and 21 kDa forms. No difference in PrPC profile was seen in human lymphocytes extracted either from spleen or tonsil. Our results highlight variations in the tissue expression profile of PrPC in bovine and human. Such differences may have an implication for PrPC function or may represent critical factors influencing the accumulation of the infectious agent in different tissues.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
