A Novel Peptide Oligomer of Bacitracin Induces M1 Macrophage Polarization by Facilitating Ca2+ Influx

Abstract

Antimicrobial peptides (AMPs) are components of the innate immune system and form the first defense against pathogens for various organisms. In the present study, we assessed whether CSP32, a novel AMP oligomer of bacitracin isolated from a strain of Bacillus spp., regulates the polarization of murine macrophage-like RAW 264.7 cells. CSP32 stimulated phagocytosis while inducing the appearance of the typical M1 polarized macrophage phenotype; these M1 macrophages play a role in host defense against pathogens. Furthermore, our results showed that CSP32 enhanced the expression and production of pro-inflammatory mediators, such as cytokines and chemokines. In addition, the CSP32-stimulated inflammatory mediators were induced mainly by the mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) signaling pathway during M1 macrophage polarization. In particular, CSP32 markedly increased the numbers of Ca2+-positive macrophages while upregulating phospholipase C and activating protein kinase Cε. Furthermore, the inhibition of intracellular Ca2+ by BAPTA-AM, a Ca2+ chelator, significantly suppressed the CSP32-mediated phagocytosis, inflammatory mediator production, and NF-κB activation. In conclusion, our data suggested that CSP32-stimulated M1 macrophage polarization is dependent on the calcium signaling pathway and may result in enhanced immune capacities.

Acidity‐Activatable Nanoparticles with Glucose Oxidase‐Enhanced Photoacoustic Imaging and Photothermal Effect, and Macrophage‐Related Immunomodulation for Synergistic Treatment of Biofilm Infection

“…[ 53 ] Nevertheless, the improvement of the polarization of proinflammatory M1 macrophages can enhance the phagocytic and bactericidal capabilities of macrophages. [ 54 ] The immunofluorescence staining images (Figure 9c) revealed that the expressions of CD86 (marker of M1 macrophage) for GB@P and GB@P+NIR were higher than PBS, PBS+NIR, B@P, and B@P+NIR, indicating that GB@P and GB@P+NIR remarkably stimulated the polarization of proinflammatory M1 macrophages, thereby enhancing the phagocytic and bactericidal effects in vivo. By contrast, the expressions of CD163 (marker of M2 macrophage) for PBS, PBS+NIR, B@P, and B@P+NIR were higher than GB@P and GB@P+NIR, indicating that PBS, PBS+NIR, B@P, and B@P+NIR remarkably stimulated the polarization of M2 macrophages, thereby decreasing the phagocytic and bactericidal capabilities in vivo.…”

Immunomodulatory Responses of Two Synthetic Peptides against Salmonella Typhimurium Infection

“…While in RAW 264.7 cells, this effect occurs by FA1 at 1.17 and from 4.69–18.75 µg/mL. FA1 also decreased the phagocytic action of both cell types at 37.5 µg/mL, which refers to a range of activity also present in other peptides [ 24 ].…”

Macrophages in aseptic loosening: Characteristics, functions, and mechanisms

“…As a result, blockade of Ca 2+ entry inhibits NF-κB/STAT1 or STAT6 signaling events and consequently lowers cytokine production that is essential for M1 or M2 polarization in macrophages ( 228 ). In detail, Ca 2+ influx facilitates M1 polarization, enabling the high productivity of proinflammatory mediators, such as cytokines and chemokines ( 229 ). Transient receptor canonical ion channel 1 (TRPC1)-mediated calcium entry seems to play a crucial role in M1 polarization, due to a non-selective TRPC1 current is found in macrophages with M1 phenotype ( 228 , 230 ).…”