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Role of Extracellular Actin and Its Clearance System in Immune Mechanisms of Disease Development

Year: 2026
Type: article
Abstract: This review focuses on the mechanisms by which extracellular actin and its clearance system components contribute to the development of pathological processes. Actin can be released from cells under conditions of stress, injury, or death. In the extracellular environment, actin exerts diverse effects on the immune and hemostatic systems. To remove excess extracellular actin, the body employs an elimination system that includes plasma gelsolin, Gc-globulin, thymosin β4, and profilin-1. The specific effect depends on the concentration of F-actin. At low, physiological concentrations—effectively managed by the clearance system—actin participates in the cross-presentation of intracellular antigens, the local stabilization of thrombi, the formation of extracellular traps, and the activity of antibacterial peptides. At higher, uncompensated concentrations, actin leads to the excessive stabilization of extracellular traps and thrombi against degradation, resulting in hyperinflammation, immunothrombosis, and increased susceptibility to infections. Furthermore, in predisposed individuals, this can lead to the development of autoantibodies against actin, contributing to various autoimmune processes. A complete loss of control over extracellular actin levels results in a sharp spike in actin concentration, causing vascular damage and obstruction, thrombosis, and, ultimately, death. Investigating the interactions between extracellular actin and the proteins responsible for its removal will help improve the diagnosis and treatment of many socially significant diseases.
Language: English
Subfield: Immunology
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7225641551
FWCI:
Cites: 317
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