Metabolic Modulation of Cell Surface Sialoform of Macrophages

Abstract

Macrophages and their precursors, monocytes, mediate the innate immune system through the initiation and regulation of inflammation and contribute to the adaptive immunity via variety mechanisms. Macrophage cell surface expresses a dense layer of glycans often terminated with sialic acids (SAs). SAs are a family of 9-carbon containing acidic monosaccharides and terminate cell surface glycans of either glycoproteins or glycolipids. The C-5-amino derivative represents the well-known neuraminic acid, and its amino functional group can be either acetylated (N-acetylneuraminic acid, Neu5Ac) or glycolylated (N-glycolylneuraminic acid, Neu5Gc). The most abundant SA is Neu5Ac. Notably, humans make Neu5Ac but are incapable of synthesizing Neu5Gc. The NeuGc deficiency in humans is attributed to a truncation in the gene encoding cytidine monophosphate sialic acid hydroxylase (CMAH). In this study, we investigated Neu5Gc incorporation of both THP-1 monocytes and THP-1 macrophages and to see its impact on macrophage functions. In addition, we designed a Neu5Gly as a Neu5Gc analog and investigated its metabolic inhibition of Neu5Gc incorporation into THP-1 monocytes and THP-1 macrophages. As a result, there is no inhibition of the Neu5Gc incorporation found when cells were treated with both Neu5Gc and Neu5Gly for both THP-1 monocytes and THP-1 macrophages, while Neu5Gly incorporation were found for both THP-1 monocytes and THP-1 macrophages. The ability to alter cell surface sialic acid structures will provide insights into structure-function relationships and the importance of individual structures in glycan-mediated processes. Further, the ability to remodel cell surface glycan architectures is expected to offer a novel approach to manipulate cellular physiology and phenotypic outcomes. Support or Funding InformationThis work was supported by Faculty Research Development Fund and the research fund from the Center for Gene Regulation in Health and Disease (GRHD) at Cleveland State University supported by Ohio Department of Development (ODOD). The authors acknowledge the National Science Foundation Major Research Instrumentation Grants for supporting NMR and QTrap 5500 mass spectrometer instrument requisition at Cleveland State University Figure 1Open in figure viewerPowerPoint Cell surface sialosides Figure 2Open in figure viewerPowerPoint Metabolic modulation of cell-surface sialic acids of monocytes and macrophages Scheme 1Open in figure viewerPowerPoint Synthesis of Zwitterionic Sialic Acid - Neu5Gly