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Electrostatic Surface Potential of Macrophages Correlates with Their Functional Phenotype

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Abstract

Macrophages exist in various functional phenotypes, which could be identified by specific surface molecules. Previous studies have shown that modulation of surface charges could alter the phagocytic function of macrophages. In this study, we show that activation of both human peripheral blood monocyte and THP-1-derived macrophages with lipopolysaccharide (LPS) or IL-1β resulted in a significant decrease in the zeta potential compared to freshly isolated monocytes and unstimulated macrophages. Interestingly, interaction with bacteria significantly increased the zeta potential of such cells irrespective of activation conditions. Similarly, IFNγ-treated pro-inflammatory macrophages showed lesser negative zeta potential compared to untreated control. A moderate reduction was also seen in IL-4-treated anti-inflammatory subtype. Additionally, in an LPS-induced systemic inflammation model, bone marrow cells isolated after 2 h of LPS injection showed significant reduction in zeta potential compared to naïve cells. Furthermore, electrostatic potential measurement of surface proteins associated with pro-inflammatory and anti-inflammatory macrophages, using in silico modeling under physiological and protonation conditions, showed that the average electrostatic potential of pro-inflammatory type surface proteins was less negative than anti-inflammatory subtype. These data suggest that the expression of different protein molecules on macrophages under different environments may contribute to the zeta potential and that this quick and low-cost technique could be used in monitoring macrophage functional phenotypes.

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Funding

We received funding from DBT-102/IFD/SAN/1671/2014-2015-PPS, DST-YSS/2015/000451-PPS, and MHRD-Supercomputing Facility Grant BT/2014-15/Plan/P-955-DS, MHRD fellowship to PC and SS, ICMR fellowship to PD, UGC fellowship to SD, and DBT fellowship to Priya and RD.

Author information

PC designed the experiments. PC, PD, SD, and Priya performed the in vitro THP-1 and primary monocyte cell differentiation and in vivo zeta potential studies and analyzed the data. PD and SS performed the in silico analysis of the molecular markers under the guidance of DS. RD and NKN created the GFP-tagged E. coli, cultured and provided the bacterial cells. PC performed the phagocytosis assay. PS conceived and directed the study. PC, PD, and PPS wrote the manuscript.

Correspondence to Pranita P. Sarangi.

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Chakraborty, P., Dipankar, P., Dash, S.P. et al. Electrostatic Surface Potential of Macrophages Correlates with Their Functional Phenotype. Inflammation (2019). https://doi.org/10.1007/s10753-019-01146-3

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KEY WORDS

  • macrophage
  • cytokine
  • inflammation
  • zeta potential
  • charge on surface proteins