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From: TSS ()
Subject: Role of gut macrophages in mice orally contaminated with scrapie or BSE
Date: June 22, 2005 at 2:13 pm PST

doi:10.1016/j.ijpharm.2005.02.042
Copyright © 2005 Elsevier B.V. All rights reserved.

Role of gut macrophages in mice orally contaminated with scrapie or BSE

Thomas Maigniena, 1, Monjed Shakwehb, 1, Pilar Calvob, Dominique Marcéa, Nicole Salèsa, c, Elias Fattalb, Jean-Philippe Deslysa, Patrick Couvreurb, , and Corinne Ida Lasmezasa

aCEA, Service de Neurovirologie, CRSSA, B.P.6, Fontenay-aux-Roses Cedex, France
bUniversité Paris-Sud, Centre d’Etudes Pharmaceutiques, UMR CNRS 8612, 5 rue Jean-Baptiste Clément, 92296 Chatenay-Malabry Cedex, France
cUniversité de Caen, UFR des Sciences Pharmaceutiques, Bd Bécquerel, 14032 Caen Cedex, France

Received 3 January 2005; revised 10 February 2005; accepted 20 February 2005. Available online 17 June 2005.


Abstract
While there is a growing consensus on the understanding of the propagation pathways after oral infection of transmissible spongiform encephalopathy (TSE) agents and even if the central role of follicular dendritic cells is identified, little is known about the key players in the first steps of the infection and about the site of the disease development. We investigated the role of gut macrophages, which are capable of capturing aggregates of the prion protein. PLGA particles containing clodronate were designed in order to be orally administered and to target Peyer's patches for inducing gut-associated macrophages suicide in mice. Mice were subsequently infected with scrapie or BSE by the oral route. It was found that the efficacy of macrophage suppression in the Peyer's patches correlated well with an earlier appearance of PrPres in these formations and with a higher amount of PrPres at a later stage of the infection. Thus, the capture of infectious particles that have crossed the epithelial gut barrier and their elimination by macrophages seems to be a key event to restrict the amount of agent initiating the infection.

Keywords: Transmissible spongiform encephalopaties; Macrophage-suicide technique; Clodronate; Peyer's patches; Intestinal uptake; Nano- and microparticles


Corresponding author. Fax: +33 1 46 61 93 34.
1 Equal contribution.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T7W-4GDSDYM-2&_coverDate=06%2F17%2F2005&_alid=289551383&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5069&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=b6c79f506bcf1cf4bb9c99a40a6e9f7b

TSS



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