AMYLOID ENHANCING FACTOR IS PRODUCED BY RATS AND AMYLOID-RESISTANT CEJ MICE/

Amyloid enhancing factor (AEF) is an operational term applied to poorl y 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 o pen the question of whether activity was dependent on the presence of amyloid fibrils or preamyloid fibril fragments. In these studies, we h ave assayed AEF activity in extracts of spleen and liver from azocasei n-injected rats and CE/J mice that do not develop amyloidosis and, hen ce, cannot have amyloid A (AA) fibrils or fibril fragments in their ti ssues. Susceptibility to amyloid induction was compared in three strai ns of mice and three strains of rats by subjecting each group of exper imental animals to multiple injections of azocasein. Spleens and liver s were removed 24 hours after the last injection, and samples of all t issues were examined for amyloid deposits. AEF was extracted from the remainder of the tissues taken from amyloid resistant CE/J mice and Sp rague-Dawley rats. Graded doses of the resulting tissue extract were g iven to naive Swiss-Webster (SW) recipient mice by i.p, injection conc omitantly 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 mu g of the CE/J-d erived AEF developed large amyloid deposits in their spleens (mean sev erity 3.7 -/+ 0.3 SEM). Lower doses (200 mu g protein) resulted in sim ilar incidence of amyloid accumulation (in four of five), but quantita tively smaller amounts of amyloid protein were present. Doses of 100 m u g decreased incidence (in one of five), whereas animals receiving 50 mu g were all negative. AEF derived from rat tissues also induced hig h incidence of amyloid (in four of five) at high doses, although the a mount of AA protein was less than in mice given equivalent amounts of CE/J mouse-derived AEF. Although 200 mu g and 100 mu g of rat AEF was effective (in two of five and one of five, respectively), 50 mu g did not result in demonstrable amyloid deposition. The presence of AEF in tissues from azocasein-treated amyloid-resistant rats and CE/J mice ex cludes the possibility that AEF activity may be due to the presence of amyloid fibrils or fibril fragments in the donor tissue.