Influence of Dextran Sulphate, Fibrin, and Ubiquitin on the Development of Casein-Induced Experimental AA Amyloidosis in C57BL/6 mice
The influence of subcutaneous injections of dextran sulphate (DS) and fibrin (F), as well as of an intraperitoneal injection of ubiquitin (Ub), was investigated on 48 male C57BL/6 mice subjected to conventional casein (C) induced amyloidosis. Histopathological examination of spleen and kidney tissue 3 and 5 weeks after termination of the amyloidogenic stimulus showed that the amount of amyloid deposited (rated trace, minimal, moderate or heavy) increased progressively with the duration of the amyloidogenic stimulus. After 3 weeks of stimulation, 16.7% of mice injected with C had some perifollicular amyloid deposits in the spleen while all had traces of amyloid in the kidney. Some amyloid was detected in the spleen of 33.3% of the mice treated with C+DS and C+Ub and 83.3% treated with C+F. Half the latter group also showed traces and half minimal amyloid deposits in their kidneys. In the other test groups, the incidence of kidney amyloidosis was less.
The most extensive tissue deposits were seen at 5 weeks postinjection (p.i.) with most in the C+F-treated animals, all showing significantly more than the control C-treated group. Thus half the C+F-treated animals had moderate and half heavy deposits throughout their spleens. Glomerulonephritis, kidney tubular edema and some amyloid deposits were present in all of the animals. C+Ub resulted in a similar incidence of amyloid accumulation in the spleen but in the kidneys 66.7% of animals had only traces of amyloid and 33.3%, minimal amyloid deposits. Amyloid was deposited in the mouse kidneys predominantly in the arterial walls but also occurred in the basement membrane and interstitial tissues. A post-mortem examination of the internal organs revealed splenomegaly in all the test groups and increased liver weight in the C-, C+F-, and C+Ub-treated groups. The leukocyte count and ESR (erythrocyte sedimentation rate) were also higher in all the experimental groups.
Thus, the results indicated that F and Ub play a role in the amyloid deposition process in the experimentally induced disorder in C57BL/6 mice and could enhance this pathological process.