SUPEROXIDE DISMUTASE-LIKE ACTIVITY OF METAL-SUBSTITUTED LACTOFERRIN DERIVATIVES

Lactoferrin (LF) is an iron-binding glycoprotein present in various se cretions including milk and the specific granules of neutrophils. The main biological properties of this protein are thought to concern the regulation of iron absorption, antimicrobial activity and modulation o f neutrophil activity. Copper bound LF (Cu-LF) inhibited the stimulati on-dependent reduction of cytochrome c (Cyt. c) in guinea pig peritone al neutrophils (GPMN) but were without effect on NADPH oxidase activit y of the respiratory burst. However, Cu-LF stimulated the stimulation- dependent production of hydrogen peroxide as seen with superoxide dism utase (SOD). Similar but weaker inhibition of Cyt. c reduction than th at shown by Cu-LF was observed with manganese-LF (Mn-LF) but not with ferrous-LF (Fe-LF) or apo-LF (Apo-LF). The inhibitory activity was con centration-dependent and the ID50s of Cu-LF and of Mn-LF were 0.1 and 5 mu M, respectively. Reactive oxygen species (ROS) detected by lumino l chemiluminescence (LCL) of stimulated-GPMN were partially inhibited by Cu-LF. Changes in LCL of stimulated GPMN induced by Cu-LF were simi lar to those of superoxide dismutase (SOD). Thus, it is concluded that low concentrations of Cu-LF had SOD-like activity and high concentrat ions of Cu-LF inhibited the stimulation-dependent generation of ROS.