The Organ Distribution of 125I‐Fibrin in the Generalized Shwartzman Reaction and its Relation to Leucocytes

Abstract

Summary. A quantitative method utilizing 125I‐fibrinogen was used to study the deposition and distribution of fibrin in the generalized Shwartzman reaction (GSR). In control rabbits, intravenous injection of 125I‐fibrinogen results in the deposition of a small quantity of radioactive material uniformly distributed among the organs examined. After two doses of endotoxin 24 hr apart, the total organ radioactivity was increased eight‐fold, most of it being found in the spleen, followed in turn by the lungs, kidneys and liver. Extraction experiments showed that the radioactive material had the characteristics of stabilized fibrin. Autoradiography of kidney slices established the characteristic features of the GSR by demonstrating localization of radioactivity in the renal glomeruli. In animals treated with warfarin, heparin, streptokinase or nitrogen mustard, little or no radioactive fibrin was found in the organs. A highly significant (P<0.001) correlation was found between the fall in leucocyte count 3 hr after the second dose of endotoxin and the amount of fibrin deposited in the organs. No corresponding correlation was found with the platelet count. The association of fibrin deposition and leucocytes was supported by expcriments with 51Cr‐labelled leucocytes which were found also to accumulate predominantly in the spleen. The findings suggest that fibrin deposition in the GSR occurs as a result of the local interaction of leucocytes with circulating fibrin monomer (FM). Accumulation of fibrin deposits is attributed to inhibition of fibrinolysis. It is concluded that the development of the GSR requires the simultaneous presence of at least three factors: FM, granulocytes and inhibition of fibrinolysis. The absence of any one of these factors is sufficient to prevent fibrin deposition in endotoxin treated animals.