Amyloid enhancing factor is produced by rats and amyloid-resistant CE/J mice.

Amyloid enhancing factor (AEF) is an operational term applied to poorly defined extracts of amyloidotic or preamyloidotic tissues capable of shortening the induction time of amyloid deposition in recipient mice from 1 to 2 weeks to 48 to 72 hours. Its derivation has always left open the question of whether activity was dependent on the presence of amyloid fibrils or preamyloid fibril fragments. In these studies, we have assayed AEF activity in extracts of spleen and liver from azocasein-injected rats and CE/J mice that do not develop amyloidosis and, hence, cannot have amyloid A (AA) fibrils or fibril fragments in their tissues. Susceptibility to amyloid induction was compared in three strains of mice and three strains of rats by subjecting each group of experimental animals to multiple injections of azocasein. Spleens and livers were removed 24 hours after the last injection, and samples of all tissues were examined for amyloid deposits. AEF was extracted from the remainder of the tissues taken from amyloid resistant CE/J mice and Sprague-Dawley rats. Graded doses of the resulting tissue extract were given to naive Swiss-Webster (SW) recipient mice by i.p. injection concomitantly with subcutaneous injection of 0.5 ml 2% AgNO3. All tissues from both CE/J mice and rat donor animals were negative for amyloid by histologic examination of Congo Red stained samples, as were the AEF extracts. All recipient mice (six of six) given 600 μg of the CE/J-derived AEF developed large amyloid deposits in their spleens (mean severity 3.7 ∓ 0.3 SEM). Lower doses (200 μg protein) resulted in similar incidence of amyloid accumulation (in four of five), but quantitatively smaller amounts of amyloid protein were present. Doses of 100 μg decreased incidence (in one of five), whereas animals receiving 50 μg were all negative. AEF derived from rat tissues also induced high incidence of amyloid (in four of five) at high doses, although the amount of AA protein was less than in mice given equivalent amounts of CE/J mouse-derived AEF. Although 200 μg and 100 μg of rat AEF was effective (in two of five and one of five, respectively), 50 μg did not result in demonstrable amyloid deposition. The presence of AEF in tissues from azocasein-treated amyloid-resistant rats and CE/J mice excludes the possibility that AEF activity may be due to the presence of amyloid fibrils or fibril fragments in the donor tissue.