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High-affinity Interactions of Beryllium (2+) with Phosphatidylserine Result in a Cross-linking Effect Reducing Surface Recognition of the Lipidстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 23 ноября 2017 г.
- Авторы: Ermakov Yu, Kamaraju K., Dunina-Barkovskaya A., Vishnyakova Kh S., Yegorov Y.E., Anishkin A., Sukharev S.
- Журнал: Biochemistry
- Том: 56
- Номер: 40
- Год издания: 2017
- Издательство: American Chemical Society
- Местоположение издательства: United States
- Первая страница: 5457
- Последняя страница: 5470
- DOI: 10.1021/acs.biochem.7b00644
- Аннотация: Abstract Beryllium has multiple industrial applications, but its manufacture is associated with serious occupational risk of developing chronic inflammation in lungs known as berylliosis, or chronic beryllium disease (CBD). Although the Be2+-induced abnormal immune responses have recently been linked to a specific MHCII allele, the nature of long-lasting granulomas is not fully understood. Here we show that Be2+ binds with a micromolar affinity to phosphatidylserine (PS), the major surface marker of apoptotic cells. Isothermal titration calorimetry (ITC) indicates that, similar to Ca2+, binding of Be2+ to PS liposomes is largely entropically driven, likely by massive desolvation. Be2+ exerts a compacting effect on PS monolayers, suggesting cross-linking through coordination by both phosphates and carboxyls in multiple configurations, which were visualized in molecular dynamics simulations. Electrostatic modification of PS membranes by Be2+ includes complete neutralization of surface charges at ~30 M, accompanied by an increase of the boundary dipole potential. The data suggests that Be2+ can displace Ca2+ from the surface of PS and, being coordinated in a tight shell of four oxygens, it can mask headgroups from Ca2+-mediated recognition by PS receptors. Indeed, 48 M Be2+ added to IC-21 cultured macrophages specifically suppresses binding and engulfment of PS-coated silica beads or aged erythrocytes. We propose that Be2+ adsorption at the surface of apoptotic cells may potentially prevent normal phagocytosis thus causing accumulation of secondary necrotic foci and the resulting chronic inflammation.
- Добавил в систему: Дунина-Барковская Антонина Яковлевна