Abstract
Macrophages play a critical role in inflammation and antigen-presentation. Abnormal macrophage function has been attributed in autoimmune diseases and cancer progression. Recent evidence suggests that high salt tissue micro-environment causes changes in macrophage activation. In our current report, we studied the role of extracellular sodium chloride on phenotype changes in peripheral circulating monocyte/macrophages collected from healthy donors. High salt (0.2M NaCl vs basal 0.1M NaCl) treatment resulted in a decrease in MΦ1 macrophage phenotype (CD11b+CD14highCD16low) from 77.4±6.2% (0.1M) to 29.3±5.7% (0.2M, p<0.05), while there was an increase in MΦ2 macrophage phenotype (CD11b+ CD14lowCD16high) from 17.2±5.9% (0.1M) to 67.4±9.4% (0.2M, p<0.05). ELISA-based cytokine analysis demonstrated that high salt treatment induced decreased expression of in the MΦ1 phenotype specific pro-inflammatory cytokine, TNFα (3.3 fold), IL-12 (2.3 fold), CCL-10 (2 fold) and CCL-5 (3.8 fold), but conversely induced an enhanced expression MΦ2-like phenotype specific anti-inflammatory cytokine, IL-10, TGFβ, CCL-17 (3.7 fold) and CCR-2 (4.3 fold). Further high salt treatment significantly decreased phagocytic efficiency of macrophages and inducible nitric oxide synthetase expression. Taken together, these data suggest that high salt extracellular environment induces an anti-inflammatory MΦ2-like macrophage phenotype with poor phagocytic and potentially reduced antigen presentation capacity commonly found in tumor microenvironment.
Highlights
Macrophages have an important role in innate immunity mediated inflammation and host defense [1]
As tolllike receptors (TLRs) are known to play a central decisive role in phagocytosis, we studied the potential changes in surface expression of TLR-2 following high salt treatment
The inflammatory phenotype of macrophages has been attributed to its inducible nitric oxide synthetase enzymatic activity and its ability to generate pro-inflammatory mediators, nitric oxide and reactive nitrogen species [19]
Summary
Macrophages have an important role in innate immunity mediated inflammation and host defense [1]. Classically activated macrophages (MΦ1) comprise immune effector cells with an acute inflammatory and phagocytic phenotype [3]. A variety of external signals, such as, microbes, damaged tissue and infiltrating lymphocytes have been shown to play an important role in the preferential MΦ1 versus MΦ2 macrophage activation. Clinical studies and experimental mouse models indicate that these macrophages generally play an anti-inflammatory and pro-tumoral role [6]. The dermal micro-environment is known to have high sodium tonicity These dermal resident macrophages have been indicated to sense the interstitial electrolyte composition and subsequently upregulate various transcription factor possibly resulting in their activation and phenotype changes [10]. In our current study, using in vitro macrophage cultures we directly determined the role of high sodium chloride concentration on macrophage phenotype changes
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