LPS-Challenged Macrophages Release Microvesicles Coated With Histones

Area of Science:

• Cell biology
• Immunology
• Molecular biology

Background:

• Histones are core components of nucleosomes and chromatin.
• Circulating histones, from cell death or NETosis, exacerbate inflammation and sepsis lethality via toll-like receptor 4 (TLR4).
• The active release mechanisms of histones by immune cells remain incompletely understood.

Purpose of the Study:

• To investigate the active release of histones by lipopolysaccharide (LPS)-activated macrophages.
• To characterize the association of released histones with extracellular vesicles.
• To determine the functional implications of vesicle-associated histones in immune signaling.

Main Methods:

• Primary macrophage cultures stimulated with LPS.
• Isolation and characterization of extracellular vesicles (EVs).
• Analysis of histone content and localization on EVs using biochemical and imaging techniques.
• Assessment of EV-associated histone interaction with toll-like receptor 4 (TLR4).

Main Results:

• LPS-activated macrophages actively release histones associated with extracellular vesicles.
• These vesicle-associated histones are exposed on the outer surface of the EVs.
• Vesicle-associated histones can interact with toll-like receptor 4 (TLR4), suggesting a signaling role.
• Histone release via EVs occurs independently of macrophage cell death.

Conclusions:

• Activated macrophages employ extracellular vesicles as a mechanism for active histone release.
• This active release contributes to the inflammatory milieu in sepsis by presenting histones to TLR4.
• Macrophage-derived EVs carrying histones may serve as danger signals, communicating infection presence and modulating immune responses.