scholarly journals Mesenchymal Stem Cell Derived Biocompatible Membrane Vesicles Demonstrate Immunomodulatory Activity Inhibiting Activation and Proliferation of Human Mononuclear Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 577
Author(s):  
Marina Gomzikova ◽  
Sevindzh Kletukhina ◽  
Sirina Kurbangaleeva ◽  
Olga Neustroeva ◽  
Olga Vasileva ◽  
...  
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
B Cells ◽  
T Lymphocytes ◽  
Mesenchymal Stem Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Membrane Vesicles ◽  
Immunomodulatory Activity ◽  
Anti Inflammatory

Immune-mediated diseases are characterized by abnormal activity of the immune system. The cytochalasin B-induced membrane vesicles (CIMVs) are innovative therapeutic instruments. However, the immunomodulating activity of human mesenchymal stem cell (MSC)-derived CIMVs (CIMVs-MSCs) remains unknown. Therefore, we sought to investigate the immunological properties of CIMVs-MSCs and evaluate their effect on human peripheral blood mononuclear cells (PBMCs). We found that CIMVs-MSCs are primarily uptaken by monocytes and B-cells. Additionally, we demonstrated that CIMVs-MSCs inhibit phytohemagglutinin (PHA)-induced proliferation of PBMCs, with more pronounced effect on T-lymphocytes expansion as compared to that of B-cells. In addition, activation of T-helpers (CD4+CD25+), B-cells (CD19+CD25+), and T-cytotoxic lymphocytes (CD8+CD25+) was also significantly suppressed by CIMVs-MSCs. Additionally, CIMVs-MSCs decreased secretion of epidermal growth factor (EGF) and pro-inflammatory Fractalkine in a population of PBMCs, while the releases of FGF-2, G-CSF, anti-inflammatory GM-CSF, MCP-3, anti-inflammatory MDC, anti-inflammatory IL-12p70, pro-inflammatory IL-1b, and MCP-1 were increased. We analyzed the effect of CIMVs-MSCs on an isolated population of CD4+ and CD8+ T-lymphocytes and demonstrated their different immune response and cytokine secretion. Finally, we observed that no xenogeneic nor allogeneic transplantation of CIMVs induced an immune response in mice. Our data suggest that CIMVs-MSCs have immunosuppressive properties, are potential agents for immunomodulating treatment, and are worthy of further investigation.

Modified Vaccinia Ankara Virus (MVA) Induces a Th1-Polarized Immune Response in Antigen-Presenting Cells (APCs).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4650-4650
Author(s):  
Christin Flechsig ◽  
Yasemin Suezer ◽  
Markus Kapp ◽  
Gerd Sutter ◽  
Hermann Einsele ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Fluorescent Protein ◽  
Conflicts Of Interest ◽  
Human Peripheral Blood ◽  
Cell Transplant ◽  
Peripheral Blood Mononuclear ◽  
Leukocyte Populations

Abstract Abstract 4650 Introduction MVA is one of the most promising vaccine candidates for infectious diseases as well as for malignancies. Astonishingly, little information exists about the mechanism by which immune responses to MVA are generated. It was shown that among leukocytes - which are essential for the generation of cellular and humoral immune responses - APCs like dendritic cells, monocytes and B cells are preferentially infected. But little is known about the effects on APCs. Therefore we wanted to analyze in more detail the general effects of MVA infections on different immune cells. Methods Primary human peripheral blood mononuclear cells (PBMCs) and isolated leukocyte populations in particular monocyte derived DCs, monocytes and B cells were infected with (wildtype) wtMVA or MVA-gfp (green fluorescent protein) to verify the infection. Subsequently changes in surface markers and cytokine expression were assessed. Results Among PBMCs and specific isolated leukocyte populations, monocytes, DCs and B cells were most susceptible to MVA infection. NK cells showed a lower and T cells a very low infection rate. Surprisingly, selected monocytes were less susceptible to MVA as compared to unselected ones. This phenomenon is due to phagocytosis of other infected PBMCs by monocytes. Furthermore we could show that MVA causes a downregulation of CD14 on iDCs and monocytes as well as of CD25, CD80, and CD86 on B cells. Furthermore, there was a slight downregulation of CD1a on iDCs and mDCs and of CD80 on iDCs. On the other hand MVA caused an upregulation of HLA-DR on monocytes and additionally a slight upregulation of CD40 on iDCs. Moreover, MVA evoked a slight upregulation of CD83 on iDCs but a slight downregulation on mDCs. Above all, we could demonstrate that MVA induces an upregulation of CXCL10 in iDCs, mDCs, monocytes, and B cells, and an upregulation of TNFα, IL-6, and IL-12p70 in iDCs, mDCs, and monocytes. In addition, we revealed a downregulation of CXCL8 in monocytes as well as of IL-β in B cells. Conclusions These results suggest that MVA induces a Th1-polarized immune response in APCs. Thus, MVA seems to be an appropriate vaccine vector for antiviral immunotherapy of stem cell transplant recipients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effects of 2-amino-4,6-di-tert-butylphenol derivatives on the viability and functional state of human peripheral blood lymphocytes

2020 ◽  
pp. 19-28
Author(s):  
Darya B. Nizheharodava ◽  
Galina A. Ksendzova ◽  
Aliaksei G. Sysa ◽  
Mariya Yu. Yurkevich ◽  
Maryna V. Labai ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Immunomodulatory Activity ◽  
Peripheral Blood Mononuclear ◽  
Blood Lymphocytes ◽  
Tert Butyl ◽  
Human Peripheral Blood Lymphocytes

Derivatives of 2-amino-4,6-di-tert-butylphenol exhibit antiviral properties and radical regulatory activity against various types of organic radicals which determines the actuality of their further investigation. But the question of aminophenol derivatives immunomodulatory activity remains open. In this regard, the aim of the study was to assess the effects of 2-amino-4,6-di-tert-butylphenol derivatives on the viability and functional potential of human peripheral blood lymphocytes. As a result of the studies, it was shown that aminophenol compounds at concentrations of 10–5–10–7 mol did not exert a toxic effect while at a concentration of 10–4 mol showed a cytotoxic effect due to the induction of secondary necrosis. Compounds N-(2-hydroxy-3,5-di-tert-butylphenyl)-4-methylbenzenesulfonamide and 2,4-di-tert-butyl-6-morpholinophenol at a concentration of 10–6 mol stimulated the extracellular production of α-interferon by peripheral blood mononuclear cells and intracellular production of γ-interferon by CD3+T-lymphocytes. An immunosuppressive effect (more than 50 %) of N-(2-hydroxy-3,5-di-tert-butylphenyl)-4-methylbenzenesulfonamide and 2,4-di-tert-butyl-6-morpholinophenol compounds at a concentration of 10–5 mol was revealed to the mitogen-induced proliferation of T-lymphocytes.

scholarly journals Peripheral blood lymphocyte receptors for B-lymphoblastoid cell lines (B-LCL)

Blood ◽  
1980 ◽  
Vol 56 (4) ◽  
pp. 690-695
Author(s):  
J Zighelboim ◽  
A Lichtenstein
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
T Lymphocytes ◽  
Cell Lines ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Wide Distribution ◽  
Lymphoblastoid Cell Lines ◽  
Surface Receptor

Because interactions between B cells and T lymphoyctes are of fundamental importance in the generation of the immune response to most antigens, we attempted to identify the cells capable of binding B- lymphoblastoid cell lines (B-LCL), their tissue distribution, and their presence in other species. Cells bearing a surface receptor for B-LCL were found in human peripheral blood, tonsil, and bone marrow, as well as mouse and rat spleen. Binding cells were phenotypically heterogeneous. The majority are T cells as defined by their ability to bind sheep red blood cells (E-rosettes). However, a subpopulation of non-T-lymphocytes were capable of binding B-LCL. This was demonstrated by depleting T cells with an E-rosette centrifugation technique and then performing a double rosette assay. The wide distribution of T lymphocytes with receptors for B-lymphoblastoid cells within peripheral lymphoid organs and their presence in several species suggest that these surface molecules may represent one of the means by which T cells and B cells interact in the induction of the immune response to T- dependent antigens.

scholarly journals Peripheral blood lymphocyte receptors for B-lymphoblastoid cell lines (B-LCL)

Blood ◽  
1980 ◽  
Vol 56 (4) ◽  
pp. 690-695 ◽  
Author(s):  
J Zighelboim ◽  
A Lichtenstein
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
T Lymphocytes ◽  
Cell Lines ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Wide Distribution ◽  
Lymphoblastoid Cell Lines ◽  
Surface Receptor

Abstract Because interactions between B cells and T lymphoyctes are of fundamental importance in the generation of the immune response to most antigens, we attempted to identify the cells capable of binding B- lymphoblastoid cell lines (B-LCL), their tissue distribution, and their presence in other species. Cells bearing a surface receptor for B-LCL were found in human peripheral blood, tonsil, and bone marrow, as well as mouse and rat spleen. Binding cells were phenotypically heterogeneous. The majority are T cells as defined by their ability to bind sheep red blood cells (E-rosettes). However, a subpopulation of non-T-lymphocytes were capable of binding B-LCL. This was demonstrated by depleting T cells with an E-rosette centrifugation technique and then performing a double rosette assay. The wide distribution of T lymphocytes with receptors for B-lymphoblastoid cells within peripheral lymphoid organs and their presence in several species suggest that these surface molecules may represent one of the means by which T cells and B cells interact in the induction of the immune response to T- dependent antigens.

scholarly journals Colonic Bacteria-Transformed Catechin Metabolite Response to Cytokine Production by Human Peripheral Blood Mononuclear Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 830 ◽  
Author(s):  
Rajapandiyan Krishnamoorthy ◽  
Abdulraheem R. Adisa ◽  
Vaiyapuri Subbarayan Periasamy ◽  
Jegan Athinarayanan ◽  
Subash-Babu Pandurangan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Immune Response ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Chromatography Mass Spectrometry ◽  
Blood Mononuclear Cells ◽  
Anti Inflammatory

Human gut microbes are a profitable tool for the modification of food compounds into biologically active metabolites. The biological properties of catechins have been extensively investigated. However, the bioavailability of catechin in human blood plasma is very low. This study aimed to determine the biotransformed catechin metabolites and their bioactive potentials for modulating the immune response of human peripheral blood mononuclear cells (PBMCs). Biotransformation of catechin was carried out using in-vitro gut microbial biotransformation method, the transformed metabolites were identified and confirmed by gas chromatography-mass spectrometry (GC–MS) and high-performance liquid chromatography-mass spectrometry (HPLC–MS). Present observations confirmed that the catechin was biotransformed into 11 metabolites upon microbial dehydroxylation and C ring cleavage. Further, immunomodulatory potential of catechin metabolites was analyzed in peripheral blood mononuclear cells (PBMCs). We found up-regulation of anti-inflammatory cytokine (IL-4, IL-10) and down-regulation of pro-inflammatory (IL-16, IL-12B) cytokine may be due to Th2 immune response. In conclusion, biotransformed catechin metabolites enhance anti-inflammatory cytokines which is beneficial for overcoming inflammatory disorders.

scholarly journals Cytokine Regulation from Human Peripheral Blood Leukocytes Cultured In Vitro with Silver Doped Bioactive Glasses Microparticles

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jefferson Muniz de Lima ◽  
Edlainne Pinheiro Ferreira ◽  
Roberta Ferreti Bonan ◽  
David Nascimento Silva-Teixeira ◽  
Luiz Ricardo Goulart ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Tissue Growth ◽  
Immunomodulatory Activity ◽  
Polymorphonuclear Cells ◽  
Bioactive Glasses ◽  
Anti Inflammatory

Bioactive glasses (BG) applications include tissue engineering for bone regeneration, coating for implants, and scaffolds for wound healing. BG can be conjugated to ions like silver, which might add some antimicrobial properties to this biomaterial. The immunomodulatory activity of ion-doped bioactive glasses particles was not investigated before. The aim of this work was to evaluate the cytotoxic and immunomodulatory effect of BG and silver-doped bioactive glass (BGAg) in human peripheral blood cells. BG and BGAg samples belonging to the system 58SiO2•(36-x)CaO·6P2O5·xAg2O, where x = 0 and 1 mol%, respectively, were synthesized via sol–gel method and characterized. Cytotoxicity, modulation of cytokine production (TNF-α, IL-1β, IL-6, IL-4, and IL-10), and oxidative stress response were investigated in human polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells (PBMCs) cultures. Cell viability in the presence of BG or BGAg was concentration-dependent. In addition, BGAg presented higher PBMCs toxicity (LC50 = 0.005%) when compared to BG (LC50 = 0.106%). Interestingly, interleukin4 was produced by PBMCs in response to BG and BGAg in absence of phytohemagglutinin (PHA) and did not modulate PHA-induced cytokine levels. Subtoxic concentrations (0.031% for BG and 0.0008% for BGAg) did not change other cytokines in PBMCs nor reactive oxygen species (ROS) production by PMN. However, BG and BGAg particles decreased zymosan-induced ROS levels in PMN. Although ion incorporation increased BG cytotoxicity, the bioactive glass particles demonstrated a in vitro anti-inflammatory potencial. Future studies are needed to clarify the scavenger potential of the BG/BGAg particles/scaffolds as well as elucidate the effect of the anti-inflammatory potential in modulating tissue growth in vivo.

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