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Abstract
High-mobility group box 1 protein (HMGB1) is a conserved protein with a variety of biological functions inside as well as outside the cell. When released by activated immune cells, it acts as a proinflammatory cytokine. Its delayed release has sparked the interest in HMGB1 as a potential therapeutic target. Here, we studied the adsorption of HMGB1 to anionic methacrylate-based polymers as well as to neutral polystyrene-divinylbenzene copolymers. Both groups of adsorbents exhibited efficient binding of recombinant HMGB1 and of HMGB1 derived from lipopolysaccharide-stimulated peripheral blood mononuclear cells. The adsorption characteristics depended on particle size, porosity, accessibility of the pores, and charge of the polymers. In addition to these physicochemical parameters of the adsorbents, modifications of the molecule itself (e.g., acetylation, phosphorylation, and oxidation), interaction with other plasma proteins or anticoagulants (e.g., heparin), or association with extracellular microvesicles may influence the binding of HMGB1 to adsorbents and lead to preferential depletion of HMGB1 subsets with different biological activity.
Highlights
High-mobility group box 1 protein (HMGB1) is a ubiquitous nonhistone DNA binding protein with distinct intra- and extracellular functions
The adsorption characteristics depended on particle size, porosity, accessibility of the pores, and charge of the polymers. In addition to these physicochemical parameters of the adsorbents, modifications of the molecule itself, interaction with other plasma proteins or anticoagulants, or association with extracellular microvesicles may influence the binding of HMGB1 to adsorbents and lead to preferential depletion of HMGB1 subsets with different biological activity
Secreted HMGB1 acts through various pattern-recognition receptors including the receptor for advanced glycation end products (RAGE), toll-like receptors TLR-2, toll-like receptor 4 (TLR-4), and TLR9, T-cell immunoglobulin domain and mucin domain 3 (TIM-3), and CXC chemokine receptor type 4 (CXCR-4) [19,20,21,22,23,24]
Summary
High-mobility group box 1 protein (HMGB1) is a ubiquitous nonhistone DNA binding protein with distinct intra- and extracellular functions. It is crucial for nuclear architecture and has been implicated in DNA replication, repair, and transcription. While the secretion of HMGB1 is regulated by phosphorylation and acetylation, its extracellular biological activity and interaction with different receptors depend on the redox. We show here that porosity, size distribution, hydrophobicity, and effective charge density as well as the distribution and accessibility of functional groups on the adsorbent surface are critical determinants of the adsorption characteristics This implies that a given polymer may preferentially bind subsets of molecules with different posttranslational or oxidative modifications and with different biological activity
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