Phagocytic Activity Of Dendritic Cells Research Articles

Combined effect of silver nanoparticles and aluminium chloride, butylparaben or diethylphthalate on the malignancy of MDA-MB-231 breast cancer cells and tumor-specific immune responses of human macrophages and monocyte-derived dendritic cells

The aim of this study was to assess whether silver nanoparticles (AgNP) or selected cosmetic ingredients may modify functions of various immunocompetent cell populations. To this end, the effect of two AgNP (size of 15 nm or 45 nm), alone and in combination with aluminium chloride, butyl paraben, di-n-butyl phthalate or diethyl phthalate was assessed on: (1) migration and invasion of MDA-MB-231 human breast cancer cells; (2) M1/M2 polarization of phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages (M0) and (3) activation/maturation of monocyte-derived dendritic cells (DCs). The results of this study showed that neither any of the test chemicals alone nor the mixtures significantly changed the migration or invasion ability of MDA-MB-231 cells following, both 72-h and 21-day exposure. Analysis of the expression of marker genes for both M1 (IL-1B, CXCL9, TNF) and M2 (DCSIGN, MRC1) polarization revealed that the chemicals/mixtures did not activate M1/M2 differentiation of the M0 macrophages. In addition, no significant changes were observed in the expression of CD86, HLA-DR and CD54 surface markers and phagocytic activity of DCs following 48-h exposure to AgNP alone or in combination with test compounds.Our study suggests that AgNP alone or in combination with tested cosmetic ingredients do not alter function of immunocompetent cells studied.

Angiotensin II Regulates Dendritic Cells through Activation of NF-κB /p65, ERK1/2 and STAT1 Pathways

Background: Activation of dendritic cells (DCs) is necessary to initiate immune responses. Angiotensin II (Ang II) has been reported to have a proinflammatory and immunomodulatory function. However, the role of Ang II in regulation of DCs and the underlying mechanisms remain illdefined. Methods: The effects of Ang II on the proliferation, maturation, phagocytosis, migration, and communication with T cells of DCs were analysed utilizing MTT, flow cytometry, ELISA, transwell assay and mixed lymphocyte culture. Results: We found that Ang II treatment significantly inhibited proliferation and phagocytic activity of DCs, but promoted the DC maturation and migration well as the expression of pro-inflammatory cytokines by DCs. In addition, Ang II also stimulated DC-mediated T cell proliferation. These effects were associated with activation of p65/NF-κB, ERK1/2 and STAT1 signaling pathways in DCs. Conclusions: Our results demonstrate that Ang II activates DCs partially through p65/NF-κB, ERK1/2 and STAT1 pathways, and suggest a potential therapeutic target of DC-mediated inflammatory disorders.

Sequential Therapy with Tenofovir Plus Peg Interferon Enhances Innate and Adaptive Immunity Compared to Tenofovir Monotherapy in Chronic Hepatitis B Patients

Viral load reduction followed by immunomodulation is an emerging approach to improve the treatment outcomes in patients with Chronic Hepatitis B (CHB). Persistent functional defects in Dendritic Cells (DC) have been observed in CHB patients, even with effective antiviral therapy. We investigated the effects of Tenofovir plus Peg-IFN Sequential Therapy (SQT) on functional restoration of innate and adaptive immunity in CHB patients. HBeAg+ve CHB patients were randomized to receive 48weeks of either tenofovir monotherapy (TM; Gr.1, n=30) or tenofovir with addition of PEG interferon from week 12 to 36 followed by tenofovir sequential therapy (SQT; Gr. 2, n=28) for 48 weeks. Biochemical parameters improved significantly with treatment at week 24 in both groups, but HBeAg seroconversion at week 48 occurred more frequently after SQT (21%) than TM (13%). At week 24, the expression and function of TLR7 and TLR9 in DCs were significantly increased in SQT compared to TM (p<0.05). Phagocytic activity of DCs, production of IFN-α and TNF-α by mDCs and pDCs and the expression of specific miRNAs for DC proliferation and maturation like miR155 and miR221, were higher in the SQT (p<0.05). After 24 weeks, SQT restored significantly more circulating CD8Tcells (p=0.02), CD8+CD127+ Tcells (p=0.03) and reduced the PD-1 expression on CD8 T-cells (p=0.04) vs. TM. Our results show that in a short period of 24 weeks, SQT significantly improves functionality of DCs. Upregulation of TLR7 and TLR9 and miR155 in DCs by PEG-IFN-α is a novel mechanism that may be quite significant in mounting an effective antiviral response. Influence of longer duration of SQT and immunomodulation needs to be studied.

Intra-Peritoneal Hyperthermia Combining α-Galactosylceramide in the Treatment of Ovarian Cancer

The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8+/IFN-γ+ tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer.

Immunomodulatory Effects of Hypocrellin A on MHC-restricted Antigen Processing

Hypocrellin A has gained much attention in recent years due to its light-induced antitumor, antifungal and antiviral activities. Here we report that hypocrellin A exerts immunomodulatory effects on MHC-restricted presentation of antigen. Hypocrellin A inhibited class II-MHC restricted presentation of exogenous antigen, but not class I MHC-restricted presentation of exogenous antigen, in dendritic cells. Hypocrellin A also inhibited the cytosolic pathway of endogenous antigen presentation. However, hypocrellin A did not inhibit the expression of class I and class II MHC molecules on dendritic cells (DCs), the phagocytic activity of DCs, or the H-2Kb-restricted presentation of a synthetic peptide, SIINFEKL. These results show that hypocrellin A differentially modulates the MHC-restricted antigen presentation pathways.

Lectins Isolated from MushroomFomitella fraxineaEnhance MHC-restricted Exogenous Antigen Presentation

Immunomodulators enhancing MHC-restricted antigen presentation would affect many cellular immune reactions mediated by T cells or T cell products. However, modulation of MHC-restricted antigen presentation has received little attention as a target for therapeutic immunoregulation. Here, we report that lectins isolated from mushroom Fomitella fraxinea enhance MHC-restricted exogenous antigen presentation in professional antigen presenting cells (APCs). Methods: Lectins, termed FFrL, were isolated from the carpophores of Fomitella fraxinea, and its effects on the class I and class II MHC-restricted presentation of exogenous ovalbumin (OVA) were examined in mouse dendritic cells (DCs) and mouse peritoneal macrophages. The effects of FFrL on the expression of total MHC molecules and the phagocytic activity were also examined in mouse DCs. Results: DCs cultured in the presence of FFrL overnight exhibited enhanced capacity in presenting exogenous OVA in association with class I and class II MHC molecules. FFrL increased slightly the total expression levels of both class I (H-2K b ) and class II (I-A b ) MHC molecules and the phagocytic activity of DCs. Antigen presentation-enhancing activity of FFrL was also observed in macrophages isolated from mouse peritoneum. Conclusion: Lectins isolated from the carpophores of Fomitella fraxinea increase MHC-restricted exogenous antigen presentation by enhancing intracellular processing events of phagocytosed antigens.

Cyclosporin A and tacrolimus, but not rapamycin, inhibit MHC-restricted antigen presentation pathways in dendritic cells

AbstractThe main targets for the immunosuppressive calcineurin inhibitors, cyclosporin A (CsA) and tacrolimus, have been considered to be activated T cells, but not antigen-presenting cells. Here we demonstrate that CsA and tacrolimus, but not rapamycin, inhibit major histocompatibility complex (MHC)–restricted antigen presentation in dendritic cells (DCs). Microencapsulated ovalbumin (OVA) was efficiently captured, processed, and presented on both class I MHC molecules (cross-presentation) as well as on class II MHC molecules. Addition of CsA and tacrolimus, but not rapamycin, to cultures of DCs inhibited both the class I processing pathway and the class II processing pathway of exogenous OVA. In addition, CsA and tacrolimus, but not rapamycin, also inhibited the classic class I processing pathway of endogenous OVA. CsA and tacrolimus did not inhibit presentation of exogenously added OVA peptide, SIINFEKL, phagocytic activity of DCs, or the total level of expression of class I MHC (H-2Kb) molecules. CsA and tacrolimus, however, inhibited profoundly the expression of SIINFEKL-H-2Kb complexes in OVA-phagocytized DCs. These results demonstrate clearly that CsA and tacrolimus inhibit intracellular processing events of antigens, and further suggest that the immunosuppressive activity of CsA and tacrolimus is at least in part due to inhibition of antigen processing pathways.

Inhibition of Major Histocompatibility Complex (MHC)-Restricted Presentation of Exogenous Antigen in Dendritic Cells by Korean Propolis Components

Dendritic cells (DCs) playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of antigen presenting cell (APC) function of DCs, we searched for and characterized APC function modulators from natural products. Methods: DCs were cultured in the presence of propolis components, WP and CP, and then examined for their ability to present exogenous antigen in association with major histocompatibility complexes (MHC). Results: WP and CP inhibited class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells, and DCs generated from bone marrow cells with GM-CSF and IL-4. The inhibitory activity of WP and CP appeared to be due not only to inhibition of phagocytic activity of DCs, but also to suppression of expression of MHC molecules on DCs. We also examined the effects of WP and CP on T cells. Interestingly, WP and CP increased IL-2 production from T cells. Conclusion: These results demonstrate that WP and CP inhibit MHC-restricted presentation of exogenous antigen through down-regulation of phagocytic activity and suppression of expression of MHC molecules on DCs.

The thyrotropin (thyroid-stimulating hormone) receptor is expressed on murine dendritic cells and on a subset of CD45RBhigh lymph node T cells: functional role for thyroid-stimulating hormone during immune activation.

Thyroid-stimulating hormone (TSH), a central neuroendocrine mediator of the hypothalamus-pituitary-thyroid axis, has been shown to affect various aspects of immunological development and function. To gain a better understanding of TSH involvement within the mammalian immune system, the expression and distribution of the TSH receptor (TSHr) has been studied by immunoprecipitation and by flow cytometric analyses. Using highly enriched populations of B cells, T cells, and dendritic cells, trace amounts of TSHr were precipitated from B cells and T cells, whereas high levels of TSHr were precipitated from the dendritic cell fraction. Flow cytometric analyses of TSHr expression on splenic and lymph node T cells revealed a major difference between those tissues in that only 2-3% of splenic T cells were TSHr+, whereas 10-20% of CD4+8- and CD4-8+ lymph node T cells expressed the TSHr, which was exclusively associated with CD45RB(high) cells and was not expressed during or after activation. The TSHr was not present on cells of the immune system during fetal or neonatal life. However, recombinant TSHbeta was found to significantly enhance the phagocytic activity of dendritic cells from adult animals and to selectively augment IL-1beta and IL-12 cytokine responses of dendritic cells following phagocytic activation. These findings identify a novel immune-endocrine bridge associated with professional APCs and naive T cells.

A life stage of particle-laden rat dendritic cells in vivo: their terminal division, active phagocytosis, and translocation from the liver to the draining lymph.

Initiation of an adoptive immune response against pathogenic organisms, such as bacteria and fungi, may involve phagocytic activity of dendritic cells (DC) or their immature precursors as a prelude to antigen processing and presentation. After intravenous injection of rats with particulate matter, particle-laden cells were detected in the peripheral hepatic lymph. Since it has been known there is a constant efflux of DC from nonlymphoid organs into the draining peripheral lymph, we examined whether these particle-laden cells belonged to the DC or macrophage lineage. The majority of particle-laden cells in lymph showed immature monocyte-like cytology, and the amount of ingested particles was small relative to typical macrophages. We identified these particle-laden cells as DC based on a number of established criteria: (a) they had a phenotype characteristic of rat DC, that is, major histocompatibility complex class Ihigh+ and IIhigh+, intercellular adhesion molecule 1+ and 80% positive with the rat DC-specific mAb OX62; (b) they showed strong stimulating capacity in primary allogeneic mixed leukocyte reaction; (c) in vitro, they had little phagocytic activity; and (d) the kinetics of translocation was similar to that of lymph DC in that they migrated to the thymus-dependent area of the regional nodes. Furthermore, bromodeoxyuridine feeding studies revealed that most of the particle-laden DC were recently produced by the terminal division of precursor cells, at least 45% of them being <5.5 d old. The particle-laden DC, defined as OX62+ latex-laden cells, were first found in the sinusoidal area of the liver, in the liver perfusate, and in spleen cell suspensions, suggesting that the site of particle capture was mainly in the blood marginating pool. It is concluded that the particle-laden cells in the hepatic lymph are recently produced immature DC that manifest a temporary phagocytic activity for intravascular particles during or after the terminal division and that the phagocytic activity is downregulated at a migratory stage when they translocate from the sinusoidal area to the hepatic lymph.