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Article Dans Une Revue Cellular Microbiology Année : 2007

Activation of classical pathway of complement cascade by soluble oligomers of prion.

Résumé

Mice defective for C1q complement factor show enhanced resistance to peripheral prion inoculation, and previous work demonstrated a direct interaction between C1q and conformationally modified PrP. However, the nature and physiological consequences of this interaction remain uncharacterized. PrP amino acids 141-159 has been identified as a potential C1q binding site; we show, by both surface plasmon resonance (SPR) spectroscopy and ELISA, that C1q and its globular region bind to PrP mutagenized in the region of interest with comparable efficiency to that of wild-type protein. To test PrP's ability to activate complement, soluble oligomers of the PrP constructs were made. Only PrP and mutagenized PrP oligomers activate the classical complement cascade while PrP monomer and the C-terminal domain, both in oligomeric and in monomeric form, failed to induce activation. This suggests that a conformational change in PrP, which occurs both when PrP is bound to an SPR sensor chip and when it undergoes oligomerization, is requisite for PrP/C1q interaction and activation of the complement cascade. We propose that C1q may act as a natural sensor for prions, leading to activation of the classical complement cascade, which could result in local inflammation and subsequent recruitment of the immune cells that prions initially infect.

Dates et versions

hal-00186753 , version 1 (12-11-2007)

Identifiants

Citer

Chantal Dumestre-Pérard, Joseph Osmundson, Catherine Lemaire-Vieille, Nicole M. Thielens, Audrey Grives, et al.. Activation of classical pathway of complement cascade by soluble oligomers of prion.. Cellular Microbiology, 2007, 9 (12), pp.2870-9. ⟨10.1111/j.1462-5822.2007.01002.x⟩. ⟨hal-00186753⟩
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