Phagocyte depletion inhibits AA amyloid accumulation in AEF-induced huIL-6 transgenic mice.
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 (125)I-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 (125)I-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.


CONCLUSIONS
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.
Department of Medicine and.
Stephen J
SJ
Kennel
Sally
S
Macy
Craig
C
Wooliver
Ying
Y
Huang
Tina
T
Richey
Eric
E
Heidel
Jonathan S
JS
Wall
D000686:Amyloidosis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D000818:Animals; D004002:Clodronic Acid / Q000008:administration & dosage; D006023:Glycoproteins; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015850:Interleukin-6 / Q000235:genetics; D008099:Liver / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010586:Phagocytes / Q000276:immunology*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014018:Tissue Distribution
D006023:Glycoproteins; C508600:IL6 protein, human; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D019275:Radiopharmaceuticals; D000685:Serum Amyloid A Protein; C046748:amyloid enhancing factor; D004002:Clodronic Acid