The Relation of the Reticulo-Endothelial System to the Formation of Amyloid

Abstract

In a recent article (1) Domagk states that he succeeded in producing amyloid in the spleen and liver of normal mice within 10 minutes by intravenous injection of a large quantity of living cocci; furthermore, that he could produce amyloid within 2 minutes in the spleen and liver of a mouse which had several injections of dead cocci previous to the final intravenous injection of living cocci. He also described marked changes in the reticulo-endothelial cells, and finally drew the conclusion that amyloid appears at first in the neighborhood of these phagocytic cells. This substance which he thought to be amyloid did not react to any of the specific stains (gentian violet or iodine), but showed metachromasia when stained with cresyl violet or Giemsa. The Influence of the Injection of Dead and Living Bacteria upon the Formation of Amyloid.Since vital staining by the intravenous injection of Congo red has proved in many experiments to be a most delicate and reliable, as well as specific, method for demonstrating even the earliest traces of amyloid (2), experiments were undertaken in order to define the nature of the substance produced in Domagk's experiments.Each of a series of 10 mice was injected with 0.2 cc. of dead streptococci in the gluteal region four times at intervals of 2 days. Following these injections 0.5 cc. of living streptococci was injected intravenously into each animal. In another series of 10 mice 0.5 cc. of living streptococci was injected intravenously without any previous injections of dead bacteria. Corresponding animals of each group were killed 15 minutes, 30 minutes, 1 hour, 2 hours, 24 hours, 2 days, 3 days and 7 days after injection. Each of these animals received 0.5-0.7 cc. of 1 per cent solution of Congo red intravenously shortly before death. 619 on

Amyloid

“…This suggests that a basically similar cellular process is operating in both the modes of amyloid induction. Our histological studies made in a situation devoid of complica tions arising from overlapping secondary effects of long term treat ments revealed some differences from as well as similarities to the observations of previous workers [13][14][15][16][17][18][19][20][21][22], T fjl u m proposed that amyl oid formation in mice (induced by 30-40 subcutaneous injections of casein) depended on the development of mesenchymal cells in two phases, namely, an initial phase characterized by a proliferation of pyroninophilic reticular and plasma cells; and a second phase charac terized by a 'suppression' of pyroninophilic cells; appearance of PASpositive material within the cytoplasm of these cells and deposition of amyloid [20,21]. C h r is t e n s e n and R a sk -N ie l s e n have also shown that pyroninophilic cells which first appear both in the splenic follicles and in marginal zones, disappear with the deposition of amyloid [18].…”

Extrusion of Amyloid Fibrils to the Extracellular Space in Experimental Mesangial AL-Amyloidosis: Transmission and Scanning Electron Microscopy Studies and Correlation with Renal Biopsy Observations

“…Initial studies dating back to 1927 emphasized the important role that macrophages play in the formation of amyloid [11]. AA-amyloidosis studies performed in the 1970s further showed a crucial role for lysosomes in the genesis of the amyloid fibrils [12][13][14][15].…”

Amyloid enhancing factor activity is associated with ubiquitin

“…Neutrophils, macrophages and reticuloendothelial (RE) cells have been associated with the forn'ation of amyloid ( Fig. 3.10,11) (Glenner 1980, K isilevsky 1983, Smetana 1927, Fuks and Zucker-Franklin 1985, Shirahama and Cohen 1975. Alkarmi and Ali-Khan 1984, Wisniewski et al 1989).…”