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  

作　　者：Eric D. Bruder John O. Richards Karen M. Michel Martin Oaks Eric D. Bruder;John O. Richards;Karen M. Michel;Martin Oaks(Transplant Research Laboratory, Aurora St. Luke’s Medical Center, Milwaukee, WI, USA)

机构地区：[1]Transplant Research Laboratory, Aurora St. Luke’s Medical Center, Milwaukee, WI, USA

出　　处：《Open Journal of Immunology》2016年第2期49-62,共14页免疫学期刊（英文）

摘　　要：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.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.

关 键 词：Anti-Inflammatory IGG IVIG MONOCYTES MACROPHAGES Sialic Acid 

分 类 号：R73[医药卫生—肿瘤]