TITLE:
Differential Effects of Alternative Glycoforms of IgG on Human Monocytes and Macrophages: Sialylated IgG Induces Novel Expression Signatures of Cell Surface Markers, Cytokines, and Chemokines
AUTHORS:
Eric D. Bruder, John O. Richards, Karen M. Michel, Martin Oaks
KEYWORDS:
Anti-Inflammatory, IgG, IVIG, Monocytes, Macrophages, Sialic Acid
JOURNAL NAME:
Open Journal of Immunology,
Vol.6 No.2,
June
9,
2016
ABSTRACT: The effector functions elicited by the fragment crystallizable (Fc) region of immunoglobulin G
(IgG) antibodies are subject to variation by the presence of terminal sialic acid (Sia) residues at
asparagine-297 (Asn-297). We have previously shown that the sialic acid-containing (Sia+) fraction
of intravenous immune globulin (IVIG) influences cell surface marker expression and cytokine/
chemokine secretion during the differentiation and maturation of human dendritic cells
(DC). The present study examined the effects of Sia+ IgG on human peripheral blood mononuclear
cell (PBMC)-derived monocyte and macrophage surface marker expression and cytokine/chemokine
secretion. Sia+ IgG induced increased expression of CD80 and dendritic cell immunoreceptor
(DCIR) on monocytes, whereas the expression of HLA-DR was decreased. In addition, the production
of IL-6, TNFα, IL-1β, and CXCL1 by monocytes was profoundly increased by treatment with
Sia+ IgG. Sia+ IgG also increased the expression of cell surface markers associated with macrophage
polarization (e.g. CD40 and CD206) on monocytes. In macrophage-colony stimulating factor (MCSF)
generated macrophages, Sia+ IgG induced increased production of numerous cytokines/
chemokines including IL-6, TNFα, CXCL1, and IL-10, and the expression of the macrophage surface
marker CD163. Our data extended prior observations of Sia+ IgG on DC function and showed that
Sia+ IgG was able to differentially modulate multiple pathways in monocytes and macrophages.
Our data indicate that the Sia+ fraction of IVIG possesses the ability to influence inflammatory processes
in multiple immune cell types and induces novel signatures in cell surface marker expression and cytokine/chemokine production.