Nancy Bigley (Advisor), Dawn Wooley (Committee Member), Marjorie Markopoulos (Committee Member)
Master of Science (MS)
Macrophages are essential phagocytic cells involved in both innate and adaptive immune systems and play vital roles in the host defense and inflammation. Macrophages have a remarkably high capacity to clear unnecessary cellular materials in interstitial environment through a process called “phagocytosis”, which is affected by many factors including suppressors of cytokine signaling (SOCS). SOCSs are a group of intracellular proteins that downregulate the cytokine signals involved in various JAK/STAT pathways through a negative feedback loop. This study focuses on investigating the effects of SOCS1 and SOCS3 on the phagocytic ability of RAW 264.7 macrophages polarized into M2a with IL-4/IL-13 and into M2c with IL-10 to clear fluorescently marked Neuro-2a malignant cells. Calreticulin (CRT) is one of the cellular signals, exposed on the surface of malignant cells, that play vital roles in controlling the phagocytosis process mediate by phagocytes including macrophages. Treatment of M2a (IL-4/IL-13) and M2c macrophages with SOCS1 peptide mimetics had no significant effects on M2a and M2c-mediated phagocytosis of CFSE-stained N2a cells compared with M2a (IL-4/IL-13) and M2c cells without SOCS1 peptide mimetic treatment, while it slightly increased the M2a (IL-4/IL-13), but not M2c, macrophage-mediated phagocytosis of N2a cells that had their calreticulin receptors blocked. When N2a cells were blocked with anti-CRT antibody, M2a and M2c-mediated phagocytosis was decreased. Interestingly, treatment of M2c with SOCS3 peptide mimetics coincided with blockage of CRT signals on N2a cells caused a significant increase in the phagocytosis of N2a cells mediated by M2c polarized macrophages. These data help to get a deeper understanding of macrophage functions in cleaning the microenvironment from apoptotic and malignant cells and even wound healing. Overall, this study sheds more light on how SOCS1/ SOCS3 can be used along with manipulation of “eat-me” signals exposed on malignant and apoptotic cells to increase the clearance rate of malignant cells and decrease the tumor survival.
Department or Program
Microbiology and Immunology
Year Degree Awarded
Copyright 2019, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.