Electrostatic Surface Potential of Macrophages Correlates with Their Functional Phenotype

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• Macrophages exhibit diverse functional phenotypes identified by surface molecules.
• Surface charge modulation, specifically zeta potential, influences macrophage phagocytic activity.
• Understanding macrophage surface properties is crucial for immune response studies.

Purpose of the Study:

• To investigate how macrophage activation and environmental interactions alter cell surface zeta potential.
• To explore the correlation between zeta potential and macrophage functional phenotypes (pro-inflammatory vs. anti-inflammatory).
• To assess the utility of zeta potential measurement as a tool for monitoring macrophage states.

Main Methods:

• Measurement of zeta potential in human peripheral blood monocytes and THP-1-derived macrophages.
• Activation of macrophages using lipopolysaccharide (LPS), IL-1β, IFNγ, and IL-4.
• Exposure of macrophages to bacteria and analysis of zeta potential changes.
• In vivo assessment using an LPS-induced systemic inflammation model in mice.
• In silico modeling of electrostatic potential for surface proteins of different macrophage subtypes.

Main Results:

• Macrophage activation with LPS or IL-1β significantly decreased zeta potential.
• Bacterial interaction increased zeta potential in activated and unactivated macrophages.
• IFNγ-treated (pro-inflammatory) macrophages exhibited a less negative zeta potential than controls.
• IL-4-treated (anti-inflammatory) macrophages showed a moderate reduction in zeta potential.
• In vivo, LPS injection led to reduced zeta potential in bone marrow cells.
• In silico analysis indicated less negative electrostatic potential for pro-inflammatory macrophage surface proteins compared to anti-inflammatory ones.

Conclusions:

• Macrophage zeta potential is dynamically altered by activation states, environmental cues (like bacteria), and functional polarization.
• Surface protein expression differences contribute to the observed zeta potential variations.
• Zeta potential measurement offers a rapid, cost-effective method for monitoring macrophage functional phenotypes.