Capacity of ceruloplasmin to scavenge products of the respiratory burst of neutrophils is not altered by the products of reactions catalyzed by myeloperoxidase

Abstract

CP is a copper-containing ferroxidase of blood plasma, which acts as an acute phase reactant during inflammation. The effect of oxidative modification of CP induced by oxidants produced by MPO, such as HOCl, HOBr, and HOSCN, on its spectral, enzymatic, and anti-inflammatory properties was studied. We monitored the chemiluminescence of lucigenin and luminol along with fluorescence of hydroethidine and scopoletin to assay the inhibition by CP of the neutrophilic respiratory burst induced by PMA or fMLP. Superoxide dismutase activity of CP and its capacity to reduce the production of oxidants in respiratory burst of neutrophils remained virtually unchanged upon modifications caused by HOCl, HOBr, and HOSCN. Meanwhile, the absorption of type I copper ions at 610 nm became reduced, along with a drop in the ferroxidase and amino oxidase activities of CP. Likewise, its inhibitory effect on the halogenating activity of MPO was diminished. Sera of either healthy donors or patients with Wilson disease were co-incubated with neutrophils from healthy volunteers. In these experiments, we observed an inverse relationship between the content of CP in sera and the rate of HO production by activated neutrophils. In conclusion, CP is likely to play a role of an anti-inflammatory factor tempering the neutrophil respiratory burst in the bloodstream despite the MPO-mediated oxidative modifications.

Metal Drugs and the Anticancer Immune Response

“…Ceruloplasmin represents a well-known acute phase protein upregulated during infection or upon trauma. , Especially regarding its role in inflammation, the complex and diverse functions of this cuproenzyme have not been clarified in detail yet. It has been described as a main inhibitor of myeloperoxidase by scavenging highly reactive oxidants generated by innate immune cells during the respiratory burst . However, ceruloplasmin might not only act anti-inflammatory via myeloperoxidase neutralization and iron starvation of the pathogen but also provide the high Cu amounts needed by macrophages upon certain infections .…”

Галлоцианин Как Флуороген Для Выявления NADPH-зависимой Продукции Супероксидного Анион-Радикала Клетками Крови

“…Остальные реактивы были производства "Реахим" (Россия) и "Белмедпрепараты" (Беларусь). Церулоплазмин (СР) выделяли из крови здоровых доноров с помощью ионообменной и аффинной хроматографии [20].…”

“…Ранее нами был предложен кинетический спектрофотометрический метод для измерения галогенирующей активности MPO, основанный на [20]. Полученные результаты позволяют предположить, что основной вклад в окисление галлоцианина в суспензии нейтрофилов происходит за счет его реакции с Следует отметить, что в крови человека подавляющее количество MPO сосредоточено в нейтрофилах и лишь незначительная ее часть -в моноцитах [1,4].…”

Celestine blue B as a sensor for hypochlorous acid and HOCL-modified proteins registration

“…CP, медь-содержащий белок плазмы крови, также ингибирует хлорирующую активность MPO за счет образования комплекса, блокируя активный центр фермента [7]. Более того, даже при модификации продуктами катализа MPO (HOCl или HOBr) ингибирующая активность CP сохраняется, в том числе по отношению к подавлению активности нейтрофилов [19,20]. Из табл.…”