High-Affinity Interactions of Beryllium(2+) with Phosphatidylserine Result in a Cross-Linking Effect Reducing Surface Recognition of the Lipid.
Biochemistry
; 56(40): 5457-5470, 2017 10 10.
Article
en En
| MEDLINE
| ID: mdl-28872302
Beryllium has multiple industrial applications, but its manufacture is associated with a serious occupational risk of developing chronic inflammation in the lungs known as berylliosis, or chronic beryllium disease. Although the Be2+-induced abnormal immune responses have recently been linked to a specific MHC-II 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 indicates that, like that of 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 â¼30 µM, accompanied by an increase in the boundary dipole potential. The data suggest 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 µM 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfatidilserinas
/
Berilio
Idioma:
En
Revista:
Biochemistry
Año:
2017
Tipo del documento:
Article
País de afiliación:
Rusia
Pais de publicación:
Estados Unidos