Cold Atmospheric Pressure Plasma Treatment Modulates Human Monocytes/Macrophages Responsiveness

Abstract

Monocytes are involved in innate immune surveillance, establishment and resolution on inflammation, and can polarize versus M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages. The possibility to control and drive immune cells activity through plasma stimulation is therefore attractive. We focused on the effects induced by cold-atmospheric plasma on human primary monocytes and monocyte-derived macrophages. Monocytes resulted more susceptible than monocyte-derived macrophages to the plasma treatment as demonstrated by the increase in reactive oxygen (ROS) production and reduction of viability. Macrophages instead were not induced to produce ROS and presented a stable viability. Analysis of macrophage markers demonstrated a time-dependent decrease of the M1 population and a correspondent increase of M2 monocyte-derived macrophages (MDM). These findings suggest that plasma treatment may drive macrophage polarization towards an anti-inflammatory phenotype.

ROS from Physical Plasmas: Redox Chemistry for Biomedical Therapy

“…Beyond the regulation of antioxidant gene expression, Nrf2 also contributes to the anti-inflammatory process by orchestrating cytokine secretion of pro- and anti-inflammatory factors, and an early infiltration and recruitment of inflammatory cells such as macrophages [142]. The regulation of most of such events, including inflammation and immune cell infiltration [123, 143, 144], depolarization of macrophages [145, 146], mitochondrial function and content [147], angiogenesis (e.g., Akt) [110, 123, 148], growth factor signalling [123, 149], and cellular viability [134, 150] are further responses after plasma treatment. Studies combining electrical fields with plasma treatment demonstrated a synergistic metabolic activation of mammalian cells [151] besides the antibacterial effect [152].…”

“…Plasma has been shown to effectively induce apoptosis in cancer cells [235–238], and it is possible that OxPL was formed in their plasma membranes. Interestingly, it has been shown that plasma favors monocyte differentiation towards a M2-like macrophage profile accompanied by an increased CD36 expression [145]. It is conceivable to think that plasma treatments could participate in both the induction of apoptosis in cancer cells and their clearance by macrophages.…”

Plasma-activated Ringer’s Lactate Solution Displays a Selective Cytotoxic Effect on Ovarian Cancer Cells

“…The pulse repetition frequency (PRF) was fixed at 1 kHz, while the peak voltage (PV) was set at 18 kV with fan always on. After plasma treatment, quantitative measurements of H 2 O 2 and NO 2 − were performed using Amplex ® Red Hydrogen Peroxide Assay Kit (Thermo Fisher Scientific #A22188, Waltham, MA, USA) and Nitrite/Nitrate colorimetric assay (ROCHE #11746081001, Basel, Switzerland) [43], respectively. In addition, before and after RL exposure to plasma, pH and conductivity were evaluated by the means of inoLab ® pH 7110 and Oakton Instrument: Con 6+ Meter, respectively.…”

Multimodal treatment combining cold atmospheric plasma and acidic fibroblast growth factor for multi‐tissue regeneration

“…In terms of dermatology, CAP can ameliorate allergic skin inflammatory disease, such as atopic dermatitis 44 . In immunology, CAP treatment of human monocytes drives the derived macrophages toward an anti‐inflammatory phenotype 45 . All in all, CAP’s anti‐inflammatory attribute alone already possesses the huge potential and is worth extensive future research.…”