During AA amyloidogenesis is proteolytic attack on serum amyloid A a pre- or post- fibrillogenic event?

Abstract

Using differential affinity chromatography, antibodies were prepared to the carboxy-terminal and amino-terminal portions of murine SAA. Immunohistochemical examinations of spleen AA amyloid with these antibodies, at both the light and electron microscopic levels, indicated the presence of epitopes from both regions of SAA in these fibrillary deposits. Whole spleen homogenates.from animals at varying periods of time following the induction of amyloidosis, were used in conjunction with electrophoresis and autoradiographic Western blotting to determine the SAA/AA ratio in spleen as a function of AA amyloid induction time. Intact SAA was a consistent constituent of splenic homogenates regardless of the time following induction. Furthermore, over a three to four week period the SAA/AA ratio gradually decreased with time. These morphologic and time course data are more consistent with SAA undergoing proteolytic cleavage after, rather than before, it is incorporated into an AA fibril.