Phagocyte depletion inhibits AA amyloid accumulation in AEF-induced huIL-6 transgenic mice

• Published in: Amyloid Vol. 21; no. 1; pp. 45 - 53
• Main Authors: Kennel, Stephen J., Macy, Sally, Wooliver, Craig, Huang, Ying, Richey, Tina, Heidel, Eric, Wall, Jonathan S.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01-03-2014; Taylor & Francis
• Subjects: AA amyloidosis; AEF; Amyloidosis - chemically induced; Amyloidosis - diagnostic imaging; Amyloidosis - immunology; Amyloidosis - therapy; Animals; clodronate liposomes; Clodronic Acid - administration & dosage; Glycoproteins; huIL-6 mice; Immunosuppression; Immunosuppressive Agents - administration & dosage; Interleukin-6 - genetics; Liver - immunology; Liver - pathology; macrophages; Mice; Mice, Transgenic; peptides; Phagocytes - immunology; Radionuclide Imaging; Radiopharmaceuticals - pharmacokinetics; SAA; Serum Amyloid A Protein - metabolism; Spleen - immunology; Spleen - pathology; Tissue Distribution
• ISSN: 1350-6129; 1744-2818
• DOI: 10.3109/13506129.2013.876400

Abstract
Objective: Determine the role of phagocytosis in the deposition of acute phase SAA protein in peripheral organs as AA amyloid.
Methods: AA amyloidosis was induced by injection of amyloid enhancing factor (AEF) in huIL-6 transgenic mice. Clodronate liposomes were injected at different times, and the amyloid load evaluated by Congo red birefringence staining and monitoring with the amyloid specific probe 125I-labeled peptide p5R.
Results: Injection of clodronate containing liposomes depleted Iba-1 positive and F4/80 positive phagocytic cells in liver and spleen for up to 5 days. Treatment prior to administration of intravenous AEF did not alter the pattern of deposition of the AEF in spleen, but inhibited the catabolism of the 125I-labeled AEF. Clodronate treatment 1 day before or 1 day after AEF administration had little effect on AA amyloid accumulation at 2 weeks; however, mice treated with clodronate liposomes 5 days after AEF induction and evaluated at 2 weeks post-AEF induction showed reduced amyloid load relative to controls. At 6 weeks post-AEF there was no significant effect on amyloid load following a single clodronate treatment.
Conclusion: Macrophages have been shown to be instrumental in both accumulation and clearance of AA amyloid after cessation of inflammation. Our data indicate that when SAA protein is continuously present, depletion of phagocytic cells during the early course of the disease progression temporarily reduces amyloid load.