Protection of ceruloplasmin by lactoferrin against hydroxyl radicals is pH dependent

Destruction of ceruloplasmin (Cp) in the presence of hydrogen peroxide is accompanied by the release of the protein's copper ions that provoke formation of hydroxyl radicals (OH) and, consequently, further degradation of the protein. Under such conditions, degradation of Cp is hampered by a number of substances able to bind copper ions. Lactoferrin (Lf) is the most active protector of Cp, its protective effect depending on the pH of the medium. The best protection of Cp by Lf was detected at pH 7.4. In an acidic buffer (pH 5.5), Lf did not affect the destruction of Cp. The pH-dependent efficiency of copper binding by Lf is in good agreement with its capacity to protect Cp against degradation provoked by hydrogen peroxide. It seems likely that peroxide-dependent degradation of Cp stimulated by its own copper ions is a part of neutrophil-induced antimicrobial reactions and may take place properly at the foci of inflammation. Interaction of Lf with Cp may regulate the generation of O[H.sup.*] from hydrogen peroxide in the foci of inflammation and protect the adjacent tissues. Key words: ceruloplasmin, lactoferrin, copper ions, hydrogen peroxide, hydroxyl radicals. La destruction de la ceruloplasmine (Cp) en presence de peroxyde d'hydrogene s'accompagne d'une liberation d'ions cuivre de la proteine ce qui provoque la formation de radicaux hydroxyles (OH-) et, consequemment, davantage de degradation de la proteine. Sous de telles conditions, la degradation de la Cp est entravee par un certain nombre de substances capables de lier les ions cuivre. La lactoferrine (Lf) est le protecteur de Cp le plus actif, son effet protecteur dependant du pH du milieu. La meilleure protection de la Cp par la Lf a ete observee a pH 7,4. La Lf n'affecte pas la destruction de la Cp dans un tampon acide (pH 5,5). L'efficacite de liaison du cuivre par la Lf dependante du pH correspond a sa capacite de proteger la Cp de la degradation provoquee par le peroxyde d'hydrogene. Il apparait probable que la degradation de la Cp dependante du peroxyde, stimulee par ses propres ions cuivre, fait partie des reactions antimicrobiennes induites par les neutrophiles et qu'elle peut se derouler adequatement aux foyers d'inflammation. L'interaction de la Lf avec la Cp peut reguler la generation de O[H.sup.*] a partir du peroxyde d'hydrogene aux foyers inflammatoires et proteger les tissus adjacents. Mots-cles: ceruloplasmine, lactoferrine, ions cuivre, peroxyde d'hydrogene, radicaux hydroxyles.
Introduction We have shown previously that the 2 metalloproteins of the acute phase of inflammation, i.e., ceruloplasmin (Cp; EC 1.16.3.1.) and lactoferrin (Lf), are able to associate in a complex [...]