Role of spleen macrophages in the clearance of scrapie agent early in pathogenesis

• Published in: The Journal of pathology Vol. 190; no. 4; pp. 495 - 502
• Main Authors: Beringue, Vincent, Demoy, Marina, Lasmézas, Corinne I., Gouritin, Bruno, Weingarten, Colette, Deslys, Jean-Philippe, Andreux, Jean-Paul, Couvreur, Patrick, Dormont, Dominique
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-03-2000; Wiley
• Subjects: Analgesics, Non-Narcotic - pharmacology; Animals; B-lymphocytes; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; clodronate; Clodronic Acid - pharmacology; Experimental viral diseases and models; follicular dendritic cells; Infectious diseases; liposomes; macrophage; Macrophages - drug effects; Macrophages - immunology; Medical sciences; Mice; Prions - metabolism; PrP; scrapie; Scrapie - immunology; Scrapie - virology; spleen; Spleen - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Viral diseases; Immunohistochemistry; Scrapie; Pathogenesis; Diphosphonic acid derivatives; Early stage; Clearance; Bisphosphonates; Degenerative disease; Spongiform encephalopathy; Spleen; Nervous system diseases; Biochemical analysis; Rodentia; Liposome; Cerebral disorder; Clodronic acid; Infection; Pathology; Vertebrata; Experimental disease; Mammalia; Mouse; Animal; Central nervous system disease; Prion; Macrophage
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/(SICI)1096-9896(200003)190:4<495::AID-PATH535>3.0.CO;2-T

The involvement of spleen macrophages in the early stages of scrapie pathogenesis was studied by applying the ‘macrophage‐suicide technique’ to scrapie‐infected mice. This method comprises critically the intravenous administration to mice of dichloromethylene disphosphonate encapsulated into liposomes. Depletion of spleen macrophages before scrapie infection induced an increased amount of scrapie inoculum in the spleen, consequently leading to accelerated scrapie agent replication in the early phase of pathogenesis, as followed by PrPres accumulation, a specific hallmark of scrapie. The same effect was observed when spleen macrophages were depleted just before the beginning of scrapie agent replication. These findings suggest that macrophages may partly control scrapie infection in peripheral tissues by sequestration of the scrapie inoculum and may thus impair early scrapie agent replication in the spleen. In addition to macrophages, most follicular dendritic cells and B lymphocytes, which are thought to support scrapie agent replication, were also transiently depleted by dichloromethylene disphosphonate administration. This suggests that a compensatory mechanism is sufficient to ensure the persistence of infection in these early stages of pathogenesis. Copyright © 2000 John Wiley & Sons, Ltd.