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Aberrations In Post-Trauma Monocyte (Mo) Subpopulation: Role In Septic Shock Syndrome, Carol Miller-Graziano, Gyongyi Szabo, Karen Kodys, Katherine Griffey
Aberrations In Post-Trauma Monocyte (Mo) Subpopulation: Role In Septic Shock Syndrome, Carol Miller-Graziano, Gyongyi Szabo, Karen Kodys, Katherine Griffey
Gyongyi Szabo
Appearance of increased proportions of monocytes bearing the 72kd(FcRI) receptor for IgG correlated to aberrant monocyte (MO) functions, depressed immune functions, and poor clinical outcome. The trauma patients' FcRI+ MO subpopulation produced the majority of their elevated IL-6, TNF alpha, TGF beta, and PGE2. IgG stimulation of patients' MO through FcRI not only stimulated TNF alpha, IL-6, and PGE2 levels, but also greatly augmented the levels of these monokines produced after subsequent bacterial challenge. Post-trauma increased IL-6 levels can lead to polyclonal B-cell activation and high levels of circulating, nonspecific IgG as seen in trauma patients. This nonspecific IgG triggers …
Role Of Elevated Monocyte Transforming Growth Factor Beta (Tgf Beta) Production In Posttrauma Immunosuppression, Carol Miller-Graziano, Gyongyi Szabo, Katherine Griffey, Bela Mehta, Karen Kodys, Donna Catalano
Role Of Elevated Monocyte Transforming Growth Factor Beta (Tgf Beta) Production In Posttrauma Immunosuppression, Carol Miller-Graziano, Gyongyi Szabo, Katherine Griffey, Bela Mehta, Karen Kodys, Donna Catalano
Gyongyi Szabo
We previously reported that increased production of prostaglandin E2 by monocytes is a pivotal mechanism in posttrauma immunopathology. Here we characterize monocyte levels of transforming growth factor beta and examine the effects of elevated transforming growth factor beta on prostaglandin E2 release by patients' monocytes. Trauma patients' and normals' monocyte supernates (+/- stimulation with muramyl dipeptide) were acid treated and assayed for transforming growth factor beta using the mink lung-cell bioassay. Alternatively, human transforming growth factor beta was added to patients' and normals' monocytes and prostaglandin E2 production assayed. Significantly elevated transforming growth factor beta levels (median = 181.7 pmol/10(6) …
Reduced Alloreactive T-Cell Activation After Alcohol Intake Is Due To Impaired Monocyte Accessory Cell Function And Correlates With Elevated Il-10, Il-13, And Decreased Ifngamma Levels, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc, Donna Catalano, Karen Kodys
Reduced Alloreactive T-Cell Activation After Alcohol Intake Is Due To Impaired Monocyte Accessory Cell Function And Correlates With Elevated Il-10, Il-13, And Decreased Ifngamma Levels, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc, Donna Catalano, Karen Kodys
Gyongyi Szabo
BACKGROUND: Immunosuppression associated with chronic alcohol use is characterized by reduced antigen-specific T-cell response and impaired delayed type hypersensitivity. Increasing evidence suggests in chronic alcohol consumption models that reduced antigen-specific T-cell proliferation is due to insufficient accessory cell function. Accessory cell function, a critical step in recognition of viral antigens, is reduced in chronic hepatitis C. The severity of hepatitis C is increased by alcohol consumption. Thus, we investigated the effects of alcohol consumption on accessory cell activity of monocytes in supporting alloreactive T-cell proliferation. METHODS: Alloreactive T-cell proliferation was evaluated in a one-way mixed lymphocyte reaction (MLR). Mononuclear cells …
Regulation Of Human Monocyte Functions By Acute Ethanol Treatment: Decreased Tumor Necrosis Factor-Alpha, Interleukin-1 Beta And Elevated Interleukin-10, And Transforming Growth Factor-Beta Production, Gyongyi Szabo, Pranoti Mandrekar, Linda Girouard, Donna Catalano
Regulation Of Human Monocyte Functions By Acute Ethanol Treatment: Decreased Tumor Necrosis Factor-Alpha, Interleukin-1 Beta And Elevated Interleukin-10, And Transforming Growth Factor-Beta Production, Gyongyi Szabo, Pranoti Mandrekar, Linda Girouard, Donna Catalano
Gyongyi Szabo
We and others have previously shown that even acute ethanol exposure has the capacity to modulate immune functions, particularly monocyte functions. Herein, we tested the hypothesis that acute ethanol treatment inhibits inflammatory, while increasing inhibitory cytokine production in human blood monocytes that, in turn, could contribute to the overall immune abnormalities seen after alcohol use. Our data show that in vitro treatment of blood monocytes with a physiologically relevant dose of alcohol (25 mM) results in significantly decreased induction of tumor necrosis factor-alpha (TNF alpha) and interleukin (IL)-1 beta by bacterial stimulation of either Gram-positive [staphylococcal enterotoxin B (SEB), 1 …
Monocytes, Alcohol Use, And Altered Immunity, Gyongyi Szabo
Monocytes, Alcohol Use, And Altered Immunity, Gyongyi Szabo
Gyongyi Szabo
The immunomodulatory capacity of acute, moderate alcohol consumption was investigated in this study in nonalcoholic volunteers after 2 ml of vodka/kg body weight of alcohol consumption. There was a significant, transient increase in interleukin-12 and interferon-gamma (IFNgamma) levels in whole blood samples collected 4 hr after alcohol consumption in response to an ex vivo bacterial challenge with lipopolysaccharide (p < 0.02). However, decreased IFNgamma levels were produced by mononuclear cells collected later after alcohol consumption (16 hr), suggesting that acute alcohol consumption has a biphasic effect on IFNgamma inducibility. Furthermore, isolated blood monocytes collected 16 hr after alcohol consumption showed significantly …
Polymorphonuclear Functions In Patients With Mixed Connective Tissue Disease, E. Bodolay, Katalin Lukacs, G. Frendl, Gyongyi Szabo, G. Arato, Gyula Szegedi
Polymorphonuclear Functions In Patients With Mixed Connective Tissue Disease, E. Bodolay, Katalin Lukacs, G. Frendl, Gyongyi Szabo, G. Arato, Gyula Szegedi
Gyongyi Szabo
Polymorphonuclear leukocytes (PMNs) from 29 patients with mixed connective tissue disease (MCTD) were studied "in vitro" for their phagocytic and chemotactic function as well as for granulocyte alkaline phosphatase (GAP) activity. Fc-receptor expression detected by EA-rosette formation was comparable to the control. Yeast-phagocytosis, C3b-receptor mediated phagocytosis and chemotaxis of PMNs, however, significantly decreased in MCTD. At the same time, photometric measure of alkaline phosphatase activity indicated a nearly two fold increase in PMNs from patients with MCTD. Although no correlation was found between PMN functions and the activity of the disease, PMN disorders may play a role in pathogenesis of …
Regulation Of Monocyte Interleukin-12 Production By Acute Alcohol: A Role For Inhibition By Interleukin-10, Linda Girouard, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo
Regulation Of Monocyte Interleukin-12 Production By Acute Alcohol: A Role For Inhibition By Interleukin-10, Linda Girouard, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo
Gyongyi Szabo
Acute ethanol treatment results in decreased antigen presentation capacity (Th1-type immunity) and elevated interleukin IL-10 (Th2 cytokine) production in human monocytes. Monocytes can contribute to both Th1 (IL-12) and Th2 (IL-10) immune responses via production of IL-12 and IL-10, respectively. Thus, we tested the hypothesis that acute alcohol treatment might affect Th1/Th2 immune balance by altering monocyte production of IL-12 and IL-10. Neither acute ethanol treatment alone (25 to 100 mM) nor its combination with a bacterial challenge Staphylococcal enterotoxin B (SEB) induced IL-12 production in isolated blood monocytes. In contrast, the same physiological alcohol concentrations increased monocyte IL-10 levels, …
Inhibition Of Antigen-Presenting Cell Functions By Alcohol: Implications For Hepatitis C Virus Infection, Gyongyi Szabo, Angela Dolganiuc, Pranoti Mandrekar, Bernadette White
Inhibition Of Antigen-Presenting Cell Functions By Alcohol: Implications For Hepatitis C Virus Infection, Gyongyi Szabo, Angela Dolganiuc, Pranoti Mandrekar, Bernadette White
Gyongyi Szabo
The mechanisms of alcohol-induced immunosuppression include defects in innate and adaptive immune responses. Monocytes and dendritic cells (DCs) link innate and adaptive immune responses as they recognize viral antigens and induce antigen-specific T-cell activation. We investigated the effects of alcohol on antigen-presenting cell functions. Acute alcohol consumption by healthy volunteers (vodka, 2 ml/kg) resulted in significantly reduced antigen-presenting cell function of monocyte-derived DCs. Reduced allostimulatory capacity of DCs treated with alcohol in vitro correlated with decreased co-stimulatory molecule (B7.1 and B7.2) expression, as well as with reduced interleukin (IL)-12 and increased IL-10 concentrations, in mixed lymphocyte cultures. Dendritic cells recognize …
Regulation Of Monocyte Il-12 Production: Augmentation By Lymphocyte Contact And Acute Ethanol Treatment, Inhibition By Elevated Intracellular Camp, Gyongyi Szabo, Linda Girouard, Pranoti Mandrekar, Donna Catalano
Regulation Of Monocyte Il-12 Production: Augmentation By Lymphocyte Contact And Acute Ethanol Treatment, Inhibition By Elevated Intracellular Camp, Gyongyi Szabo, Linda Girouard, Pranoti Mandrekar, Donna Catalano
Gyongyi Szabo
IL-12, a monocyte-derived cytokine, is pivotal in activation of cellular immune response and inflammation. Both inflammatory response and cellular immunity are impaired by acute ethanol consumption. Here, we found that in vitro acute ethanol treatment (25-100 mM) results in a dose-dependent and significant increase of IL-12 in IFN-gamma (100 U/ml) plus Staphylococcal enterotoxin B (SEB; 1 microg/ml) stimulated monocytes and mononuclear cells but not in unstimulated cells from non-alcoholic blood donors. There was significantly greater IL-12 production in the MNC population compared to isolated Mphi (P < 0.001). Prevention of monocyte surface contact with either purified T lymphocytes or monocyte-depleted MNC resulted in a significant, 65+/-20%, decrease in IL-12 production regardless of IFN-gamma, SEB or ethanol stimulation suggesting that Mphi T-cell surface contact provides an additional signal for IL-12 production. In addition to cell surface contact, soluble mediators, particularly IL-10 and PGE2 may regulate IL-12 production. The cyclooxygenase inhibitor, Indomethacin (10(-6)M), augmented both IL-12 and IL-10 levels in isolated monocytes and mononuclear cells whether induced by medium, SEB or SEB plus 25 mM ethanol suggesting that regulation of IL-12 production via the cyclooxygenase pathway is independent of IL-10. Finally, elevation of intracellular cAMP levels by dbcAMP treatment consistently inhibited IL-12 as well as IL-10 production in monocytes induced by IFN-gamma or IFN-gamma plus 25 mM ethanol. These data suggest that augmentation of monocyte IL-12 by acute ethanol is not mediated via the cAMP pathway.
Ethanol-Mediated Regulation Of Transcription Factors In Immunocompetent Cells, Gyongyi Szabo, Pranoti Mandrekar
Ethanol-Mediated Regulation Of Transcription Factors In Immunocompetent Cells, Gyongyi Szabo, Pranoti Mandrekar
Gyongyi Szabo
The immunomodulatory effects of acute and chronic alcohol use are characterized by impaired antigen-specific immune activation and by increased susceptibility to infections due to alterations in innate immune responses and inflammatory mediator production. The central feature of cellular responses to inflammatory and stress signals is the activation of the nuclear regulatory kappa B/Rel family of transcriptional factors via various surface receptor systems in immunocompetent cells. Activation of NF-kappa B, however, is regulated at multiple levels including I-kappa B degradation, nuclear translocation, and by interaction of NF-kappa B/Rel with other transcription factors. Data from our and other laboratories demonstrate that acute …
Stimulating Effect Of Tuftsin And Its Analogues On The Defective Monocyte Chemotaxis In Systemic Lupus Erythematosus, Katalin Lukacs, Gyongyi Szabo, Ildiko Sonkoly, Eva Vegh, Janos Gacs, Maria Szekerke, Gyula Szegedi
Stimulating Effect Of Tuftsin And Its Analogues On The Defective Monocyte Chemotaxis In Systemic Lupus Erythematosus, Katalin Lukacs, Gyongyi Szabo, Ildiko Sonkoly, Eva Vegh, Janos Gacs, Maria Szekerke, Gyula Szegedi
Gyongyi Szabo
Monocytes and macrophages are engaged at various levels of cellular immune reactivity. In addition to their function in the defensive mechanism directed at infective agents, they also play a basic role in immune complex elimination and antigen handling. Previous experiments revealed that systemic lupus erythematosus (SLE), the main representative of the autoimmune diseases, is associated with impaired monocyte chemotaxis. The endogenous basic tetrapeptide tuftsin and 6 of its analogues were examined in vitro for their stimulating capacity on the chemotactic responsiveness of monocytes derived from patients with SLE. The monocyte migration assay was carried out by a modified Boyden technique …
Acute Ethanol Treatment Modulates Toll-Like Receptor-4 Association With Lipid Rafts, Angela Dolganiuc, Genadyi Bakis, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo
Acute Ethanol Treatment Modulates Toll-Like Receptor-4 Association With Lipid Rafts, Angela Dolganiuc, Genadyi Bakis, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo
Gyongyi Szabo
BACKGROUND: Alcohol, a substance that is most frequently abused, suppresses innate immune responses to microbial pathogens. The host senses pathogens via Toll-like receptors (TLRs). Recent studies indicate that alcohol affects TLR signaling. METHODS: Here, we hypothesized that acute alcohol treatment may interfere with early steps of membrane-associated TLR2 and TLR4 signaling at the level of lipid rafts. Human monocytes and Chinese hamster ovary (CHO) cells, transfected with human TLR2, TLR4, or CD14, were stimulated with peptidoglycan (PGN, TLR2 ligand) or lipopolysaccharide (LPS, TLR4 ligand) with or without alcohol (50 mM) and analyzed for cytokine production (enzyme-linked immunosorbent assay), nuclear factor-kappaB …