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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

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Open Journal of Immunology 2016年第2期6卷 49-62页

作者： Eric D. Bruder John O. Richards Karen M. Michel Martin Oaks Transplant Research Laboratory Aurora St. Luke’s Medical Center Milwaukee WI USA

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

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Activation of human monocytes/macrophages by OHR/AVR118 promotes both pro- and Anti-Inflammatory phenotypes

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Advances in Bioscience and Biotechnology 2014年第3期5卷 161-168页

作者： Shalom Z. Hirchman OHR Pharmaceutical Inc. New York USA

The immunomodulator OHR/AVR118 has been shown to increase IL-8 and MCP-1 secretion from non-activated human monocytes and U937 pro-monocytic cells, but to decrease MCP-1 secretion from LPS-activated monocytes, suggesting its effect depends on immune cell environment and/or activation state. We therefore assessed the effect of OHR/AVR118 on cytokine secretion by human PBMCs and adherent monocytes. OHR/AVR118 increased IL-6, IL-1β, and TNF-α secretion byPHA/IL-2-primed PBMCs, but did not alter IL-12 secretion. In contrast, treatment of LPS-activated monocytes decreased TNF-α and IL-12, increased IL-6, but did not alter IL-1β, secretion. To further show that the effect of OHR/AVR118 depends on cellular environment, we monitored U937 differentiation towards mature macrophages in the presence of drug. OHR/AVR118 promoted a pro-inflammatory response in PMA-activated cells, as demonstrated by increased expression of the maturation markers CD86, CD32, and CD87 and by increased IL-8, MCP-1, and GM-CSF secretion. In undifferentiated U937 cells, OHR/AVR118 did not alter phagocytosis of opsonized S. aureus and IL-10 secretion. Whereas, after activation, OHR/AVR118 induced an anti-inflammatory phenotype, as indicated by reduced phagocytosis and increased IL-10 secretion. Overall, these findings suggest that OHR/AVR118 has a dual action on monocyte/macrophage function depending on cellular activation state, resulting in either further activation or suppression.

关键词： Peptide-Nucleic Acid monocytes Chemokines Cytokines Inflammation

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c-Met identifies a population of matrix metalloproteinases 9-producing monocytes accumulated in the peritumoral stroma of human hepatocellular carcinoma

c-Met identifies a population of matrix metalloproteinases 9...

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第九届全国免疫学学术大会

作者： Lan Zhao Yan Wu Limin Zheng Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory of BiocontrolSun Yat-sen University

Macrophages(Mφ)are prominent components of solid tumors and exhibit distinct phenotypes in different *** have recently found that tumors can alter the normal developmental process of Mφto trigger transient activation of monocytes in the peritumoral stroma of human hepatocellular carcinoma(HCC).In the present study,we showed that a fraction of monocytes in peritumoral stroma,but not in cancer nests,expresses surface c-Met molecules in tumors from patients with *** activated by tumors strongly express c-Met proteins with kinetics similar to theiractivation status,and significant correlations were found between the levels of c-Met and HLA-DR on tumor-infiltrating ***-κB-mediated autocrine TNF-αstimulated the expression of c-Met on acitivated monocyte,and c-Met in turn,regulates the retention,accumulation,and production of matrix metalloproteinases(MMP)9 by monocytes in the peritumoral stroma of HCC after engaging with its ligand ***,the expression of c-met on activated monocytes/Mφmay represent a novel mechanism that tumor precisely positioned these cells to perform specific functions in situ to facilitate tumor progression.

关键词： c-Met monocytes Hepatocellular carcinoma

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Melatonin improves diets induced NASH through inhibiting CCR3+ monocytes proinflammation

Melatonin improves diets induced NASH through inhibiting CCR...

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第十四届全国免疫学学术大会

作者： guangyong sun yaning wang lu yang dong zhang Beijing Friendship Hospital Capital Medical University

Background and Aims:Nonalcoholic steatohepatitis(NASH) has become one of the leading causes of end-stage liver ***,there is no approved therapy for *** inflammation is the driving force for the development and progression of *** has been reported to have immunoregulatory effects on both innate and adaptive *** this study,we aim to evaluate the potential application and its underlying mechanisms of melatonin in the treatment of ***:In a methionine and choline deficient diet(MCD)-fed NASH model,the C57 BL/6 mice received melatonin(100 g/***) by oral gavage for 4 *** development was confirmed by *** transcriptome landscape of intrahepatic macrophages of mice which received with or without melatonin were evaluated by single-cell mRNA ***:Compared with control mice,MCD-fed mice with melatonin intervention exhibited significantly lowered levels of plasma ALT and AST,decreased liver steatosis,lobular inflammation and focal liver *** treatment mainly inhibited CD11F4/80 monocytes liver infiltration,TNF-alpha secretion and MHC Ⅱ expression during NASH ***,no significant difference in the frequency of Kupffer cells and liver infiltrated lymphocytes from MCD-fed mice treated with or without melatonin was ***-cell mRNA sequencing identified 10 distinct liver infiltrated monocyte clusters in MCD-fed *** 3 pro-inflammatory intrahepatic monocyte clusters,the administration of melatonin selectively inhibited a unique monocyte subset that highly expressed Ccr3 and pro-inflammatory related genes,such as Retnlg,Sema7 a,Cxcl2,G0 s2 and ***,melatonin might inhibit Ccr3monocyte proinflammation mainly through downregulating oxidative stress in endoplasmic reticulum of ***:We elucidates that melatonin selectively inhibits CCR3monocytes,a unique intrahepatic monocyte cluster pro-inflammation and improves diets induced NASH

关键词： nonalcoholic steatohepatitis melatonin monocytes inflammation

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Arsenic trioxide inhibites transgenic tumor necrosis factor-α promoter activity in vascular smooth muscle cells and THP-1 monocytes in vitro

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Journal of Chinese Pharmaceutical Sciences 2007年第2期16卷 134-138页

作者：张卓琦曹希传黄永麟徐州医学院附属医院心内科江苏徐州221002 中国矿业大学材料学院江苏徐州221009 哈尔滨医科大学第一临床医学院心内科黑龙江哈尔滨150001

Aim This study was to evaluate the effect of arsenic trioxide （As2O3） on the transgenic TNF-α promoter activity in cultured vascular smooth muscle cells （VSMCs） and THP-1 monocytes. Methods Human TNF-α promoter was constructed by reporter gene system and was transiently transfected into VSMCs and THP-1 in vitro. The promoter activity was tested by luciferase activity with or without LPS and Ang Ⅱ stimulation, before and after different dosage of As2O3 treatment. Results 1. TNF-α promoter effectively expressed in VSMCs and THP-1 compared with CMV promoter （58.3% and 80.9%, respectively）. Both LPS and Ang Ⅱ significantly up-regulated TNF-α promoter activity （P〈0.05）. 2. As2O3 significantly inhibited, both intact and LPS/Ang Ⅱ stimulated promoter activity, in a dose dependent manner （P〈0.05）, and in both cell type. Conclusion These results manifested that, the inhibition effect of As2O3 on the activity of human TNF-α promoter indicated its potential inhibition on pro-inflammatory cytokine genes expression at transcriptional level and its potential anti-inflammatory property in the cardiovascular system.

关键词： Arsenic trioxide TNF-α promoter Inflammation Smooth muscle cells Vascular monocytes

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Endotoxin Tolerance Mediates a Global Change in the Epigenetic Landscape of monocytes

Endotoxin Tolerance Mediates a Global Change in the Epigenet...

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第十届全国免疫学学术大会

作者： C.Reschke C.Walter P.Hansen D.M.Ibrahim J.Fischer K.Jürchott J.Hecht H.Volk G.Grütz Max Planck Institute for Molecular Genetics

The phenomenon by which monocytes and other immune cells render tolerant after repetitive exposure to LPS is known as endotoxin *** tolerance induction has a high clinical impact in sepsis patients,where a systemic tolerization of the immune system to invading pathogens and their components makes the patients more susceptible to secondary infections.

关键词： Epigenetics endotoxin tolerance monocytes

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Activated monocytes expand interleukin-21-producing CD4+ T cells and create conditions for hepatocellular carcinoma progression

Activated monocytes expand interleukin-21-producing CD4+ T c...

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第十四届全国肿瘤生物治疗大会

作者：陈敏敏肖肖郑利民邝栋明 Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University

Although cancer patients exhibit a generalized immunosuppressive status, substantial evidence indicates that the inflammatory reaction at a tumor site can promote tumor growth and progression. Hepatocellular carcinoma(HCC) is usually derived from inflamed cirrhotic liver with extensive leukocyte infiltration. Here we show that interleukin(IL)-21-producing CD4+ T cells were enriched predominantly in the peritumoral stroma of HCC tissues, and their levels were well correlated with monocyte/macrophage density in the same area. Most peritumoral CD68+ cells exhibited an activated phenotype. Accordingly, tumor-activated monocytes played an important role in inducing expansion of IL-21-producing CD4+ T cells from circulating memory T cells in vitro with phenotypic features similar to those isolated from HCCs. Moreover, we found that tumor-activated monocytes secreted a set of key proinflammatory cytokines that triggered proliferation of functional IL-21-producing cells. Importantly, we found that the IL-21-producing CD4+ T cells operated in IL-21–IFN-γ-dependent pathways to induce plasma cell differentiation and thereby create conditions for HCC progression.

关键词： monocytes interleukin-21 hepatocellular carcinoma

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IFN-γ Down-regulated CXCR2 Expression on Circulating monocytes Results in Re-education of Tumor-Associated Macrophages in Colorectal Cancer

IFN-γ Down-regulated CXCR2 Expression on Circulating Monocy...

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第十四届全国免疫学学术大会

作者： Huayang Wang Qilu Hospital of Shandong Universtiy

Objective:Circulating monocytes are important resources of tumor-associated macrophages(TAMs),but their recruitment to tumor tissue and further differentiation remain not fully *** receptors play essential roles in cancer development and anti-tumor immunity *** the present study,we explored the expression of CXCR2 on circulating monocytes and its roles in biological functions of monocytes and tumor-associated ***:Colorectal cancer(CRC) patients and healthy volunteers were recruited and peripheral blood were collected before ***2 expression on circulating monocytes were analyzed by flow ***2 expression level on circulating monocytes were analyzed with clinicopathological characteristics of CRC *** of pro-inflammatory cytokines in serum were analyzed by ***2 knock-down was performed on THP-1 monocyte line by transfecting lentivirus-loading *** behaviors of monocyte/macrophages,including migration,secretion and phagocytosis,were analyzed in CXCR2-KD or control ***:We observed a significant decrease of CXCR2 expression on classical(CD14CD16) circulating monocytes of colorectal cancer(CRC) *** positive rate of CXCR2 on classical monocytes were significantly decreased in CRC patients with lymph node involvement and/or *** percentage of CXCR2classical monocytes were positively correlated with inflammatory markers(CRP,ESR and Glascow prognostic score) and serum inflammatory cytokines,but negatively with local inflammatory status in ***-inflammatory cytokine IFN-y was over-expressed in CRC patients and was involved in CXCR2 downregulation by promoting GRK-2 expression in *** CXCR2 expression was associated with impeded recruitment of monocytes toward tumor,secretion of pro-inflammatory cytokines,and phagocytosis of CRC-educated ***2-KDTAMs exhibited different phenotypes with control ***:In summary,our findings s

关键词： Colorectal cancer monocytes CXCR2 Interferon-γ Tumor-associated macrophages

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c-Met identifies a population of matrix metalloproteinase 9-producing monocytes in peritumoral stroma of hepatocellular carcinoma

c-Met identifies a population of matrix metalloproteinase 9-...

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第十四届全国肿瘤生物治疗大会

作者：赵蓝吴艳郑利民 Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University

Macrophages(Mφ) are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. Previously, we found that tumors could alter the normal developmental process of Mφ to trigger transient activation of monocytes in the peritumoral stroma of human hepatocellular carcinoma(HCC). In the present study, we showed that a fraction of monocytes in the peritumoral stroma, but not in HCC cancer nests, expressed surface c-Met molecules. monocytes exposed to tumors strongly expressed c-Met proteins with kinetics similar to their activation status, and significant correlations were found between c-Met levels and HLA-DR expression on tumor-infiltrating monocytes. NF-κB-mediated autocrine TNF-α stimulated the expression of c-Met on activated monocytes, and by interacting with its ligand HGF, c-Met regulated the retention, accumulation, and matrix metalloproteinase(MMP) 9-producing capacity of monocytes in the peritumoral stroma of HCC. The intensity of c-Met expression on tumor-infiltrating monocytes was associated with high mortality and reduced survival of patients with HCC. Therefore, the expression of c-Met on activated monocytes/Mφ may represent a novel mechanism by which a tumor actively and precisely regulates the distribution and functions of these cells to facilitate disease progression.

关键词： c-Met monocytes matrix metalloproteinase 9 hepatocellular carcinoma

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Galectin Hco-gal-m from Haemonchus contortus modulates goat monocytes and T cell function in different patterns

Galectin Hco-gal-m from Haemonchus contortus modulates goat ...

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中国畜牧兽医学会兽医寄生虫学分会第十三次学术研讨会

作者：王望 Shuai Wang Hui Zhang Cheng Yuan RuoFeng Yan XiaoKai Song LiXin Xu 李祥瑞南京农业大学动物医学院

Background:monocytes and T cells are two major subpopulations of peripheral blood mononuclear cells(PBMC) and play an essential role in the innate and adaptive immune *** members of the galectin family show multiple and distinct regulatory effects on different cell *** studies have demonstrated that the galectin from Haemonchus contortus(Hco-gal-m) performed immunomodulatory effects on goat PBMC,however,which subpopulation of PBMC is the primary target of Hco-gal-m and whether the immune modulations share the same mechanism remain ***:In this study,the developmental expression of Hco-gal-m was analyzed by RT-PCR and Western blot *** distribution of Hco-gal-m in adult worm was detected by an immunohistochemical *** bmding activity of the recombinant Hco-gal-m(rHco-gal-m) on goat monocytes and T cells were assessed by flow *** immunomodulatory effects of Hco-gal-m on cytokine secretion,cell activation and apoptosis were observed by co-incubation of rHco-gal-m with goat monocytes and T ***:Hco-gal-m was expressed in L4 as well as adult worms and predominantly localized at the internal surface of the worm ***-gal-m could bind to both monocytes and T *** engagement of rHco-gal-m decreased the production of IL-6,IL-10 and TNF-α in T cells,however,it significantly increased the secretion of IL-10 in *** rHco-gal-m exposure,the expression of MHC-Ⅱ on monocytes and that of CD25 on T cells were ***,T cell proliferations were potently inhibited by *** addition,rHco-gal-m induced apoptosis in T cells,but not significantly in ***:Our results indicated that rHco-gal-m modulated goat monocytes and T cell function in different patterns.

关键词： Haemonchus contortus Galectin PBMC monocytes T cells

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