دانلود رایگان مقاله تحریک MΦ2 فنوتیپ مانند ضد التهابی در ماکروفاژهای محیطی

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 (0.2 M NaCl vs basal 0.1 M NaCl) treatment resulted in a decrease in MΦ1 macrophage phenotype (CD11bþCD14highCD16low) from 77.476.2% (0.1 M) to 29.375.7% (0.2 M, po0.05), while there was an increase in MΦ2 macrophage phenotype (CD11bþ CD14lowCD16high) from 17.275.9% (0.1 M) to 67.479.4% (0.2 M, po0.05). ELISAbased 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 antiinflammatory 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 antiinflammatory MΦ2-like macrophage phenotype with poor phagocytic and potentially reduced antigen presentation capacity commonly found in tumor microenvironment.

4. Discussion

\An inflammatory component is present in the microenvironment of most tumors. Several lines of evidence have led to a generally accepted paradigm that inflammation and cancer are interlinked. Macrophages are a heterogeneous population of innate myeloid cells involved in inflammatory responses [20]. Macrophages have different functions, and different transcriptional profiles, but all are required to maintain homeostasis. Studies in mice showed that a distinct population of macrophages helps to disperse malignant cells to survive and grow in distant sites. Tumor associated macrophages (TAMs) play an important role in tumor immunity and show similar functions to MΦ2 phenotype [4]. TAMs are a polarized MΦ2 macrophage population with potent immunosuppressive functions [21]. The predominant expression of these M2 macrophages reflects the late stage of tumor progression and poor outcome. Several surface markers have been attributed to the M1/M2 phenotype and is also dependent upon the tissue microenvironment [22]. In particular, the difference in the expression of lipopolysaccharide-binding-receptor (CD14) and of Fcγ receptor III (CD16) has been used to distinguish various MO subpopulations [23]. The majority (70–90%) of peripheral blood MO consists of cells strongly CD14 positive and CD16 negative (CD14þCD16- ) and are usually regarded as ‘classical activated’. The remaining MO express CD16 but have different expression levels of CD14 which are predominantly regarded as alternately activated [24].