http://hdl.handle.net/20.500.12323/5721 2026-04-03T08:39:16Z 2026-04-03T08:39:16Z Халилова, И.С. Гельфгат, Е.Б. Джохаридзе, Т.З. Джавадов, С.А. http://hdl.handle.net/20.500.12323/7719 2024-11-05T07:42:12Z 1993-01-01T00:00:00Z

Title: Сравнительное изучение основных параметров иммуного статуса и антител к инсулину у больных сахарном диабетом Authors: Халилова, И.С.; Гельфгат, Е.Б.; Джохаридзе, Т.З.; Джавадов, С.А.

1993-01-01T00:00:00Z Халилова, И.С. Джохаридзе, Т.З. Гельфгат, Е.Б. Джавадов, С.А. http://hdl.handle.net/20.500.12323/7718 2024-11-05T07:36:46Z 1994-01-01T00:00:00Z

Title: Разработка экспериментальной модели иммуносорбента для удаления антител к инсулину из плазмы крови Authors: Халилова, И.С.; Джохаридзе, Т.З.; Гельфгат, Е.Б.; Джавадов, С.А.

1994-01-01T00:00:00Z Chapman, Anna L. P. Mocatta, Tessa J. Shiva, Sruti Seidel, Antonia Chen, Brian Khalilova, Irada Paumann-Page, Martina E. Jameson, Guy N. L. Winterbourn, Christine C. Kettle, Anthony J. http://hdl.handle.net/20.500.12323/7405 2024-03-18T10:46:56Z 2013-01-10T00:00:00Z

Title: Ceruloplasmin Is an Endogenous Inhibitor of Myeloperoxidase Authors: Chapman, Anna L. P.; Mocatta, Tessa J.; Shiva, Sruti; Seidel, Antonia; Chen, Brian; Khalilova, Irada; Paumann-Page, Martina E.; Jameson, Guy N. L.; Winterbourn, Christine C.; Kettle, Anthony J. Abstract: Myeloperoxidase is a neutrophil enzyme that promotes oxidative stress in numerous inflammatory pathologies. It uses hydrogen peroxide to catalyze the production of strong oxidants including chlorine bleach and free radicals. A physiological defense against the inappropriate action of this enzyme has yet to be identified. We found that myeloperoxidase oxidized 75% of the ascorbate in plasma from ceruloplasmin knock-out mice, but there was no significant loss in plasma from wild type animals. When myeloperoxidase was added to human plasma it became bound to other proteins and was reversibly inhibited. Ceruloplasmin was the predominant protein associated with myeloperoxidase. When the purified proteins were mixed, they became strongly but reversibly associated. Ceruloplasmin was a potent inhibitor of purified myeloperoxidase, inhibiting production of hypochlorous acid by 50% at 25 nm. Ceruloplasmin rapidly reduced Compound I, the Fe(V) redox intermediate of myeloperoxidase, to Compound II, which has Fe(IV) in its heme prosthetic groups. It also prevented the fast reduction of Compound II by tyrosine. In the presence of chloride and hydrogen peroxide, ceruloplasmin converted myeloperoxidase to Compound II and slowed its conversion back to the ferric enzyme. Collectively, our results indicate that ceruloplasmin inhibits myeloperoxidase by reducing Compound I and then trapping the enzyme as inactive Compound II. We propose that ceruloplasmin should provide a protective shield against inadvertent oxidant production by myeloperoxidase during inflammation.

2013-01-10T00:00:00Z Paumann-Page, Martina V. Ashby, Louisa Khalilova, Irada Magon, Nicholas J. Hofbauer, Stefan Paton, Louise N. Furtmüller, Paul G. Obinger, Christian Kettle, Anthony J. http://hdl.handle.net/20.500.12323/6791 2023-09-04T09:05:13Z 2023-12-01T00:00:00Z

Title: Hypochlorous acid inactivates myeloperoxidase inside phagocytosing neutrophils Authors: Paumann-Page, Martina; V. Ashby, Louisa; Khalilova, Irada; Magon, Nicholas J.; Hofbauer, Stefan; Paton, Louise N.; Furtmüller, Paul G.; Obinger, Christian; Kettle, Anthony J. Abstract: When neutrophils phagocytose bacteria, they release myeloperoxidase (MPO) into phagosomes to catalyse the conversion of superoxide to the potent antimicrobial oxidant hypochlorous acid (HOCl). Here we show that within neutrophils, MPO is inactivated by HOCl. In this study, we aimed to identify the effects of HOCl on the structure and function of MPO, and determine the enzyme’s susceptibility to oxidative inactivation during phagocytosis. When hydrogen peroxide was added to a neutrophil granule extract containing chloride, MPO activity was rapidly lost in a HOCl-dependent reaction. With high concentrations of hydrogen peroxide, western blotting demonstrated that MPO was both fragmented and converted to high molecular weight aggregates. Using the purified enzyme, we showed that HOCl generated by MPO inactivated the enzyme by destroying its prosthetic heme groups and releasing iron. MPO protein was additionally modified by forming high molecular weight aggregates. Before inactivation occurred, MPO chlorinated itself to convert most of its amine groups to dichloramines. When human neutrophils phagocytosed Staphylococcus aureus, they released MPO that was largely inactivated in a process that required production of superoxide. Enzyme inactivation occurred inside neutrophils because it was not blocked when extracellular HOCl was scavenged with methionine. The inactivated enzyme contained a chlorinated tyrosine residue, establishing that it had reacted with HOCl. Our results demonstrate that MPO will substantially inactivate itself during phagocytosis, which may limit oxidant production inside phagosomes. Other neutrophil proteins are also likely to be inactivated. The chloramines formed on neutrophil proteins may contribute to the bactericidal milieu of the phagosome.

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