Inhibiting Serum Amyloid P - FcɣR1 Interactions on Human Macrophages Decreases Numbers of Intracellular Mycobacteria
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Macrophages are a heterogeneous population of cells and, include classically activated macrophages (M1) and alternatively activated macrophages (M2). Macrophages can change from M1 to M2 and vice versa in response to environmental stimuli. Serum Amyloid P (SAP) is a constitutive plasma protein that polarizes macrophages to an M2 phenotype, and part of this effect is mediated through FcγRI receptors. In an effort to find ways to alter macrophage phenotypes, we screened for compounds that can block the SAP- FcγRI interaction. From a screen of 3000 compounds, we found 12 compounds that reduced the ability of fluorescently labeled human SAP to bind cells expressing human FcγRI. Based on cell surface marker expression, 8 of the compounds inhibited the effect of SAP on skewing human macrophages to an M2 phenotype and in the presence of SAP polarized macrophages to an M1 phenotype. In diseases such as tuberculosis, M1 macrophages are more effective at killing bacteria than M2 macrophages. SAP potentiated the numbers of the mycobacterial strains M. smegmatis and M. tuberculosis in macrophages. When added along with SAP, 2 of the compounds reduced intracellular mycobacterium numbers. Together, these results indicate that blocking SAP effects on macrophages can skew these cells toward a M1 phenotype, and this may be useful in treating diseases such as tuberculosis.
Xiang, Wang (2018). Inhibiting Serum Amyloid P - FcɣR1 Interactions on Human Macrophages Decreases Numbers of Intracellular Mycobacteria. Master's thesis, Texas A & M University. Available electronically from