Sofia N Nyström1, Gunilla T Westermark. 1. Department of Clinical and Experimental Medicine, Division of Cell Biology, Linköping University, Linköping, Sweden.
Abstract
OBJECTIVE: AA amyloidosis is a complication to longstanding inflammatory diseases, but reduction of amyloid mass has been reported as the inflammation ceases. Not much is known about the endogenous factors that contribute to this amyloid resolution. Herein, we describe the dynamics of amyloid degradation and resolution in experimental murine AA-amyloidosis. METHODS: AA-amyloidosis was induced in mice with injections of amyloid enhancing factor (AEF) and by inflammation induced with injections of silver nitrate. Resolution of amyloid deposits was monitored over time. RESULTS: Virtually all amyloid was cleared within 34 weeks. Using the ELISA-technique, antibodies directed against protein AA were detected in animals during amyloid clearance phase and macrophages were shown to internalize amyloid. Also, passive immunization with an amyloid specific monoclonal antibody, produced by a B-cell clone recovered from an animal with advanced AA-amyloidosis, reduced amyloid development in murine AA-amyloidosis. CONCLUSION: Immunoglobulins co-localize with amyloid deposits and can contribute to amyloid degradation by Fc-receptor mediated phagocytosis, and should be considered key players in the degradation process.
OBJECTIVE: AA amyloidosis is a complication to longstanding inflammatory diseases, but reduction of amyloid mass has been reported as the inflammation ceases. Not much is known about the endogenous factors that contribute to this amyloid resolution. Herein, we describe the dynamics of amyloid degradation and resolution in experimental murineAA-amyloidosis. METHODS:AA-amyloidosis was induced in mice with injections of amyloid enhancing factor (AEF) and by inflammation induced with injections of silver nitrate. Resolution of amyloid deposits was monitored over time. RESULTS: Virtually all amyloid was cleared within 34 weeks. Using the ELISA-technique, antibodies directed against protein AA were detected in animals during amyloid clearance phase and macrophages were shown to internalize amyloid. Also, passive immunization with an amyloid specific monoclonal antibody, produced by a B-cell clone recovered from an animal with advanced AA-amyloidosis, reduced amyloid development in murineAA-amyloidosis. CONCLUSION: Immunoglobulins co-localize with amyloid deposits and can contribute to amyloid degradation by Fc-receptor mediated phagocytosis, and should be considered key players in the degradation process.
Authors: Tina Richey; James S Foster; Angela D Williams; Anna B Williams; Alexa Stroh; Sallie Macy; Craig Wooliver; R Eric Heidel; Siva K Varanasi; Elizabeth N Ergen; Dianne J Trent; Stephen A Kania; Stephen J Kennel; Emily B Martin; Jonathan S Wall Journal: Am J Pathol Date: 2019-02-06 Impact factor: 4.307
Authors: M Ankarcrona; B Winblad; C Monteiro; C Fearns; E T Powers; J Johansson; G T Westermark; J Presto; B-G Ericzon; J W Kelly Journal: J Intern Med Date: 2016-05-10 Impact factor: 8.989
Authors: Stephen J Kennel; Sally Macy; Craig Wooliver; Ying Huang; Tina Richey; Eric Heidel; Jonathan S Wall Journal: Amyloid Date: 2014-01-22 Impact factor: 7.141
Authors: James S Foster; Angela D Williams; Sallie Macy; Tina Richey; Alan Stuckey; Daniel Craig Wooliver; Richa Koul-Tiwari; Emily B Martin; Stephen J Kennel; Jonathan S Wall Journal: Front Immunol Date: 2017-09-04 Impact factor: 7.561
Authors: Désirée S Jansson; Caroline Bröjer; Aleksija Neimanis; Torsten Mörner; Charles L Murphy; Faruk Otman; Per Westermark Journal: PLoS One Date: 2018-03-01 Impact factor: 3.240