Alpha 1 acid glycoprotein (α1-AGP) is an acute-phase protein, and its plasma levels are increased in patients with severe burn injuries and various cancers. It has been reported that α1-AGP has an ability to polarize macrophages (MΦ) from resident MΦ to M2MΦ (IL-10+IL-12− MΦ, an immunosuppressive MΦ with reduced capacity to kill pathogens or cancer cells). So far, three subsets of M2MΦ (M2aMΦ, M2bMΦ and M2cMΦ) have been described. All 3 subsets of M2MΦ are equally immunosuppressive. In this study, resident monocytes (CD14+IL-10−IL-12− cells) cultured with α1-AGP were demonstrated to be specifically converted to M2bMΦ. Healthy donor monocytes cultured for 24 to 72 hrs with 0.0625 to 4.0 mg/ml of α1-AGP produced CCL1 (a biomarker of M2bMΦ) into their culture fluids. The maximum CCL1 production was demonstrated when resident monocytes were stimulated with 4 mg/ml of α1-AGP. Similar to RPMI 1640 medium supplemented with heat-inactivated FBS, CCL1 was produced by healthy donor monocytes stimulated with α1-AGP in serum-free medium cultures. However, CCL17 (a biomarker of M2a monocytes) and CXCL13 (a biomarker of M2c monocytes) were not detected in their culture fluids. Also, these monocytes did not express DC-SIGN (a biomarker of M2a monocytes) and showed weak bactericidal activities against P. aeruginosa and E. faecalis. These results indicate that the MΦ conversion from resident MΦ to M2bMΦ is specifically stimulated by α1-AGP .
- Copyright © 2013 by The American Association of Immunologists, Inc.