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Acta Pharmacologica Sinica 2004年第10期 121-125页

作者： Xiao-hui JI, Ting YAO, Jun-chuan QIN, Shu-kui WANG, Hui-juan WANG, Kun YAOMicrobiology and Immunology Institute of Nanjing Medical University, Nanjing 210029 National Key Laboratory of Medical Pharmaceutical Biotechnology, Nanjing University, Nanjing 210008 The First Hospital of Nanjing Affiliated to Nanjing Medical University, Nanjing 210006, China

AIM: To Study the interaction of macrophage colony-stimulating factor (M-CSF) and interleukin-10 (IL-10) in productions of IL-12 and IL-18 and expressions of CD14, CD23, and CD64 by human monocytes. METHODS: Purified adherent human monocytes were cultured with M-CSF or IL-10 alone, or with M-CSF+IL-10 and 2-3d later, the culture supernatants and cells were separated and collected. IL-12P40 and IL-18 levels in the superna-tants were determined by ELISA and the percentages of CD14, CD23, and CD64 positive cells were examined by flow cytometry. RESULTS: (1) IL-10 decreased M-CSF-induced IL-18 levels, while M-CSF further reduced IL-12P40 level in the culture supernatants of IL-10-treated monocytes; (2) IL-10 alone had no effect on the percentage of CD14-positive cells, but further increased the percentage of CD14-positive cells induced by M-CSF; M-CSF alone had no effect on the percentage of CD64-positive cells, but further increased the percentage of CD64-positive cells induced by IL-10; (3) IL-10 decreased

关键词： macrophage colony-stimulating factor interleukin-10 monocytes cytokines membrane molecule

Expression of Monocyte Chemoattractant Protein-1 in monocytes and Effects of Native and Oxidized Very Low Density Lipoproteins

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1997年第4期17卷 203-205页

作者：王国平邓仲端倪娟 Department of Pathology Tongji Medical University Wuhan

Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capacity of human peripheral blood monocytes to express MCP-1 and effects of native very low density lipoprotein (VLDL) and oxidized VLDL(OX-VLDL) on the expression. The total RNA was extracted from cultured monocytes, which were exposed to VLDL and OX-VLDL, and the media conditioned by monocytes were collected. MCP-1 mRNA expression was examined by Northern blot analysis. MCP-1 protein in conditioned media was determined by using sandwich ELISA. The results showed that monocytes can express MCP-1 after a 24 h incubation at 37℃，and the expression was markedly increased by a exposure to OX-VLDL, whereas the expression was slightly increased when exposed to VLDL. It suggests that the capacity of monocytes to produce MCP-1 that recruits and activates circulating monocytes may be of considerable importance in atherogenesis, and oxidation of VLDL enhances its potential to promote atherogenesis.

关键词： monocyte chemoattractant protein-1 very low density lipoprotein oxidization monocytes atherosclerosis

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

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

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

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

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

Melatonin improves diets induced NASH through inhibiting CCR3+ monocytes proinflammation

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Melatonin improves diets induced NASH through inhibiting CCR...

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

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

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

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

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

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

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

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

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

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

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

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

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