Proteolysis of ceruloplasmin and copper transfer to lactoferrin

Acute phase reactants ceruloplasmin (CP), a copper protein, and lactoferrin, (LF), an iron protein, form a complex both in vitro and in vivo [Zakharova et al., 2000]. Limited proteolysis facilitates release of copper ions from CP, which may have its deleterious effect in foci of inflammation. We were interested to study whether LF associated with CP affects its proteolysis and loss of copper. Neutrophil proteases elastase and cathepsin G efficiently cleave CP. Along with CP these two proteases are found in increased concentrations in the foci of inflammation where the share of proteolyzed CP may also increase. Incubation of apo-LF/CP complex with trypsin resulted in limited proteolysis of CP, while LF remained intact. Copper ions released from CP were incorporated in increasing amounts by apo-LF, which was evidenced by concomitant decrease of CP absorption at 610 nm and increase of the band at 435 nm corresponding to Cu-LF. Apo-LF did not incorporate, copper ions if CP was intact. The observed mechanism might be of importance for protection against pro-oxidative transition metals in the foci of inflammation.