DURING AA-AMYLOIDOGENESIS IS PROTEOLYTIC ATTACK ON SERUM AMYLOID-A A PRE-FIBRILLOGENIC OR POST-FIBRILLOGENIC EVENT

Using differential affinity chromatography, antibodies were prepared t o the carboxy-terminal and amino-terminal portions of murine SAA. Immu nohistochemical examinations of spleen AA amyloid with these antibodie s at both the light and electron microscopic levels, indicated the pre sence of epitopes from both regions of SAA in these fibrillary deposit s. Whole spleen homogenates, from animals at varying periods of time f ollowing the induction of amyloidosis, were used in conjunction with e lectrophoresis and autoradiographic Western blotting to determine the SAA/AA ratio in spleen as a function of AA amyloid induction rime. int act SAA was a consistent constituent of splenic homogenates regardless of the time following induction. Furthermore, over a three to four we ek period the SAA/AA ratio gradually decreased with time. These morpho logic and time course data are more consistent with SAA undergoing pro teolytic cleavage after I after than before, it is incorporated into a n AA fibril.