Brefeldin A inhibits experimentally induced AA amyloidosis.
OBJECTIVE
Brefeldin A, an antibiotic with effects on certain intracellular compartments, was tested on murine secondary AA amyloidosis. Effects on splenic proteoglycan metabolism were analyzed along with plasma serum amyloid A (SAA) levels.


METHODS
Brefeldin A was administered daily to mice undergoing inflammatory stimulation with complete Freund's adjuvant to induce reactive AA amyloidosis. AA amyloid deposition was assessed using histochemistry, immunohistochemistry, and electron microscopy. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting were used to detect SAA in acute phase serum. Relative (semiquantitative) measurements of total SAA levels were obtained by densitometry of stained gels. Splenic proteoglycan metabolism was analyzed in treated animals and compared to untreated individuals by in vivo 35S administration during amyloid fibrillogenesis.


RESULTS
Based on (immuno)histochemistry and electron microscopy, animals undergoing drug treatment did not develop splenic amyloidosis, whereas the control animals exhibited massive amyloid fibril deposits in the spleen (p < 0.001). SAA was detected at roughly equal quantities in serum from both groups. No significant qualitative or quantitative difference in proteoglycan synthesis was found.


CONCLUSIONS
Brefeldin A seems to exert an inhibitory action on murine AA amyloidosis. It appears that the effect does not depend on the lack of fibril protein precursor nor altered proteoglycan synthesis.
Stenstad
T
T
Department of Rheumatology, University of Tromsø, Norway.
Husby
G
G
D000686:Amyloidosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D020126:Brefeldin A; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005620:Freund's Adjuvant; D007150:Immunohistochemistry; D051379:Mice; D008808:Mice, Inbred CBA; D008854:Microscopy, Electron; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D013154:Spleen / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure
D003517:Cyclopentanes; D011500:Protein Synthesis Inhibitors; D000685:Serum Amyloid A Protein; D020126:Brefeldin A; D005620:Freund's Adjuvant