Inhibition of soluble immune response suppressor activity by growth factors.

Extracellular vesicles that are shed from the plasma membranes take an active part in intercellular communication, transporting a wide range of molecules, including proteins, lipids, nucleic acids and carbohydrates, being of great functional importance. One of the steps to better understanding of distant communications of cells and their regulatory mechanisms is a proteomic study of various extracellular vesicles, including microvesicles and exosomes. Pro-inflammatory cytokines produced by monocytes and individual complement system components play a key role in their specific functioning. The aim of this work was to study proteomic composition of THP-1 monocyte-like cells and their microvesicles. The MALDI-mass spectrometric analysis of electrophoretic protein fractions of cell lysates and microvesicles allowed for identifying 107 proteins that perform various functions. Among 19 determined functional groups, the largest ones comprise transcription regulators and proteins with unknown functions. The smallest functional groups include regulators of cell differentiation and development, proteins participating in immune response and inflammation, cellular receptors and their regulators, transporter and transport regulatory proteins, as well as cell proteins mediating adhesion and matrix structures, processing regulators, proteins of ubiquitin-proteasome system, intracellular signaling, autophagy and exocytosis regulators, chromatin structural proteins, hemostatic regulators, and peptide hormones. An intermediate position is occupied by cytokines and growth factors, enzymes, cytoskeleton and motor proteins, as well as RNA processing and translation regulators. The subsequent DAVID Functional Annotation Clustering analysis allowed for identifying the most common groups distributed by their molecular function, biological processes, and cellular component. Separately, in the microvesicles derived from THP-1 monocyte-like cells, proteins of the immune response and inflammation, cytokines and growth factors, intracellular signaling proteins, cell differentiation regulators and developmental proteins, as well as cell adhesion and matrix proteins were identified among other protein molecules. The data obtained on the partial proteome of THP-1 monocyte-like cells and their microvesicles extend the existing knowledge on distant communications between the cells and suggest new mechanisms of interaction between monocytes/macrophages and their microenvironment.

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CD38 and Regulation of the Immune Response Cells in Cancer

Journal of Oncology ◽

10.1155/2021/6630295 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Sanyog Dwivedi ◽

Erika P. Rendón-Huerta ◽

Vianney Ortiz-Navarrete ◽

Luis F. Montaño

Keyword(s):

Immune Response ◽

Cancer Progression ◽

Immune Escape ◽

Transmembrane Protein ◽

Suppressor Cells ◽

Typical Feature ◽

Metabolic Reprogramming ◽

Suppressor Activity ◽

Nad Glycohydrolase ◽

Cell Mediated Immune Response

Cancer is a leading cause of death worldwide. Understanding the functional mechanisms associated with metabolic reprogramming, which is a typical feature of cancer cells, is key to effective therapy. CD38, primarily a NAD + glycohydrolase and ADPR cyclase, is a multifunctional transmembrane protein whose abnormal overexpression in a variety of tumor types is associated with cancer progression. It is linked to VEGFR2 mediated angiogenesis and immune suppression as it favors the recruitment of suppressive immune cells like Tregs and myeloid-derived suppressor cells, thus helping immune escape. CD38 is expressed in M1 macrophages and in neutrophil and T cell-mediated immune response and is associated with IFNγ-mediated suppressor activity of immune responses. Targeting CD38 with anti-CD38 monoclonal antibodies in hematological malignancies has shown excellent results. Bearing that in mind, targeting CD38 in other nonhematological cancer types, especially carcinomas, which are of epithelial origin with specific anti-CD38 antibodies alone or in combination with immunomodulatory drugs, is an interesting option that deserves profound consideration.

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Development of the LAFTI range of probiotic cultures

Microbiology Australia ◽

10.1071/ma03132 ◽

2003 ◽

Vol 24 (1) ◽

pp. 32

Author(s):

M L Harvey ◽

A Henriksson ◽

N W Dunn

Keyword(s):

Immune Response ◽

Growth Factors ◽

Mixed Cultures ◽

Beneficial Effects ◽

Cholesterol Levels ◽

Indigenous Microflora ◽

Starch Production ◽

Stimulation Of

Probiotics are mono or mixed cultures of live microorganisms which, when applied to man or animal, beneficially affect the host by improving the properties of the indigenous microflora. Some of the beneficial effects that a probiotic culture can have on its host include improved digestion and absorption of various nutrients (e.g. lactose, starch), production of vitamins and growth factors, protection against pathogens, stimulation of the immune response, reduction of cholesterol levels and reduction of diarrhoea.

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Immune status in bronchopulmonary dysplasia

Kazan medical journal ◽

10.17750/kmj2016-346 ◽

2016 ◽

Vol 97 (3) ◽

pp. 346-350 ◽

Cited By ~ 1

Author(s):

I A Mustafayev ◽

L I Allakhverdieva ◽

A V Bogdanova

Keyword(s):

Immune Response ◽

Bronchopulmonary Dysplasia ◽

Reference Values ◽

Immune Complexes ◽

Interferon Γ ◽

Circulating Immune Complexes ◽

Interleukin 4 ◽

Reference Ranges ◽

Suppressor Activity ◽

Remission Phase

Aim. To study cell-mediated and humoral immunity in bronchopulmonary dysplasia in children.Methods. The inpatient and outpatient medical records of 103 children from the 1st day of life up to 3 years of age: 58 boys and 45 girls, were analyzed. T-lymphocytes helper and suppressor activity markers, the immunoregulatory index, B-lymphocytes markers, concentration of the three main immunoglobulins classes, pro- and anti-inflammatory interleukins, circulating immune complexes were determined.Results.. The helper activity in exacerbation phase was at the lower limit of normal (42.1±0.9) and significantly increased in remission phase (52.6±0.8), without exceeding the reference values. CD8 lymphocytes percentage in the blood remained within the reference ranges both in exacerbation of inflammation and in remission phase. Immunoregulatory index was above normal both in the exacerbation and in the remission phases, reducing in remission phase. Pro-inflammatory interleukin-4 concentration in the exacerbation period exceeded reference values by 1.5 times and amounted to 21.0±0.6 pg/ml. In the remission phase its normalization (11.1±0.4 pg/ml) appeared. Interleukin-8 and interferon-γ levels in the exacerbation stage were significantly higher than normal and amounted to 70.3±1.2 and 15.1±0.4 pg/ml, respectively. The tumor necrosis factor concentration was at the upper limit of normal (19.54±0.29 pg/ml). The humoral immune response was characterized by a slight decrease in the immunoglobulin A level, some increase in immunoglobulin G and a significant increase in the circulating immune complexes concentration (109.5±6.6 units) in the exacerbation phase.Conclusion. Pronounced immunosuppression is uncharacteristic for bronchopulmonary dysplasia; identified changes are an adequate immune response to viral and bacterial infection in the acute phase of disease.

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EFFECT OF OIL CONTAINING n-3 POLYUNSATURATED FATTY ACIDS (PUFA) ON THE IMMUNE RESPONSE AND GROWTH FACTORS IN PIGLETS

Acta Veterinaria Hungarica ◽

10.1556/avet.47.1999.3.6 ◽

1999 ◽

Vol 47 (3) ◽

pp. 325-334 ◽

Cited By ~ 4

Author(s):

Viera Revajová ◽

D. Magic ◽

M. Levkut ◽

Ĺ. Bindas ◽

M. Horváth ◽

...

Keyword(s):

Fatty Acids ◽

Immune Response ◽

Growth Factors ◽

Oral Administration ◽

Polyunsaturated Fatty Acids ◽

Metabolic Activity ◽

Peripheral Blood ◽

Inflammatory Processes ◽

The Individual ◽

Experimental Group

Oral administration of n-3 polyunsaturated fatty acids (PUFA) to piglets slightly enhances the immune response. As compared to the control, in the experimental piglets the absolute values of monocytes in the peripheral blood were significantly increased (P < 0.05), while the metabolic activity of phagocytes and the number of lymphocytes within the individual subpopulations were slightly higher. The level of growth factors, determined on the basis of somatomedin in the blood serum, was significantly higher in the experimental group (P < 0.05). n-3 PUFA interfere with the synthesis of prostaglandins and influence the metabolism of fatty acids. This finding may contribute to the therapy of inflammatory processes influencing immune and growth factors in piglets.

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Genetically-Engineered Endothelial Cells Implanted Into the Omentum of Hemophilia A Dogs Provides Long-Term Circulating FVIII Resulting From Sustained FVIII Expression and Persistent Cell Viability.

Blood ◽

10.1182/blood.v114.22.3578.3578 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3578-3578 ◽

Cited By ~ 2

Author(s):

Margareth C Ozelo ◽

Hideto Matsui ◽

Carol A. Hegadorn ◽

Lori Harpell ◽

Sandra Powell ◽

...

Keyword(s):

Immune Response ◽

Endothelial Cells ◽

Growth Factors ◽

Cell Viability ◽

Hemophilia A ◽

Lentiviral Vector ◽

Ex Vivo ◽

Autologous Blood ◽

Cell Transplant ◽

Therapy Strategy

Abstract Abstract 3578 Poster Board III-515 Ex vivo delivery of therapeutic transgenes provides an additional level of safety as it avoids systemic administration of viral vectors. Our group has shown that autologous blood outgrowth endothelial cells (BOECs) transduced with a lentiviral vector delivery system containing the FVIII transgene is a promising gene therapy strategy for hemophilia A. We have shown that subcutaneous implantation of factor (F) VIII-expressing BOECs in a murine model of hemophilia A can produce therapeutic levels of FVIII that are sustained for more than 6 months. However, to improve the levels of FVIII expression and cell viability we wanted to evaluate the omentum as an alternative site for BOEC implantation. Initially this strategy was evaluated in two normal dogs. One and three months after delivery of the cells, immunostaining of biopsies from the injection sites showed the presence of viable cells expressing FVIII and evidence of neovascularization. To evaluate the efficacy of this strategy, a hemophilia A dog received 5×108 transduced autologous BOECs that expressed high levels of FVIII in vitro (1.5 IU/106 cells/24hrs). We used autologous fibrinogen as a vehicle for the cells along with canine endothelial growth factors (VEGF and bFGF). For the implantation procedure the dog received prophylaxis with canine cryoprecipitate transfusions. FVIII antigen levels (FVIII:Ag) of between 20 and 50 ng/mL continue to be detected in the plasma 8 months post-implantation, indicating that these cells remain viable and express persistent high levels of FVIII over an extended period of time. However, two weeks after the procedure, the dog developed an anti-FVIII immune response comprising both inhibitory and non-inhibitory antibodies, and therefore no FVIII coagulant activity (FVIII:C) was detected. With a view to preventing the development of the anti-FVIII immune response, we used immunosuppression with cyclophosphamide in two additional hemophilia A dogs. Each of these dogs received 5 × 108 transduced autologous BOECs. In place of fibrinogen, these cells were delivered in a gel comprised of synthetic, heparin-binding peptide-amphiphiles (HBPA) and heparan sulfate, along with canine VEGF and bFGF. The peptide gel prolongs the activity of these growth factors and protects them from proteolysis, enhancing their angiogenic activity. HBPA gel has been shown to increase vascularization of cell transplant sites, which should improve BOEC survival in the omentum. The procedure of implanting the genetically modified BOECs was completed without complications in all hemophilia A dogs and we are continuing to evaluate the efficacy of this strategy. Disclosures: Hulvat: Nanotope Inc.: Employment.

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Analysis of T cell hybridomas. I. Characterization of H-2 and Igh-restricted monoclonal suppressor factors.

Journal of Experimental Medicine ◽

10.1084/jem.154.5.1390 ◽

1981 ◽

Vol 154 (5) ◽

pp. 1390-1402 ◽

Cited By ~ 37

Author(s):

M Minami ◽

K Okuda ◽

S Furusawa ◽

B Benacerraf ◽

M E Dorf

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Cell Lines ◽

Immune Suppression ◽

Cellular Interactions ◽

Suppressor T Cells ◽

Suppressor Activity ◽

T Cell Lines

Five hybridoma T cell lines were prepared by fusion of second order suppressor T cells (Ts2) with the BW5147 thymoma. The culture supernates from these T cell hybrids contained a factor, TsF2, which specifically suppressed 4-hydroxy-3-nitrophenyl acetyl hapten (NP)-induced cutaneous sensitivity responses. TsF2 activity was observed when the factor was administered during the effector phases of the immune response. TsF2 bears I-J determinants and has binding specificity for NPb idiotypic determinants. TsF2 suppressor activity could be absorbed on antigen-primed H-2-incompatible T cells but cannot suppress H-2-incompatible mice. In addition to this H-2 restriction, which maps to the I-J subregion, monoclonal TsF2 also has an Igh genetic restriction. The present results are combined with previous data to describe the cellular interactions leading to immune suppression.

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