Bernard S Brown

Aggregation of fibrinogen molecules by metal ions

The ability of metal ions to cause physical aggregation of neutral solutions of bovine fibrinogen has been studied. Three categories were found: (a) ions (such as Ca2+, Mg2+ and Mn2+) which did not cause aggregation even when present in 1–100 mm concentrations: (b) ions (such as Fe2+, Cu2+ and Ni2+) which caused aggregation in the 0–10 mm concentration range, (c) ions (such as Hg2+, Zn2+, Cr3+, La3+) which caused aggregation in the 0–1000 μm concentration range. Aggregation occurs immediately the metal ion is brought into contact with the fibrinogen, and product formation reaches a steady state within 5 min. With the exception of Zn2+, all the ions that caused aggregation exhibited a threshold concentration below which no observable aggregation took place. The threshold concentration for Hg2+, the most effective ion studied, was 6 μm. Addition of excess EDTA caused resolubilization of the aggregated fibrinogen due to removal of the metal ions. Aggregation is thus thought to be a physical process initiated by binding of metal ions to those carboxyl groups in fibrinogen responsible for keeping the monomers apart in solution. The aggregation does not involve prior proteolytic degradation of the fibrinogen.

EVIDENCE FOR CARRIAGE OF SILVER BY SULPHADIMIDINE: HAEMOLYSIS OF HUMAN ERYTHROCYTES

1 Human erythrocytes suspended in isotonic saline haemolyse in the presence of both Ag+ ions and sulphadimidine. 2 Neither Ag+ ions nor sulphadimidine on their own will haemolyse erythrocytes suspended in isotonic saline. 3 At constant Ag+ ion concentration the degree of haemolysis of saline‐suspended erythrocytes depends upon the concentration of sulphadimidine. 4 Human erythrocytes suspended in isotonic sucrose (chloride‐free) haemolyse in the presence of Ag+ ions. 5 Sulphadimidine in chloride‐free sucrose competes with erythrocytes for Ag+ ions resulting in stoichiometric protection of the erythrocytes from the haemolytic action of Ag+ ions. 6 Haemolysis occurs when each erythrocyte receives approximately 1.2 × 109 Ag+ ions whether suspended in saline or sucrose. 7 Sulphadimidine acts as a carrier for Ag+ ions and so prevents their precipitation as AgCl when erythrocytes are suspended in saline.