During the past decade, investigators have evaluated the role of hematopoietic growth factors as cytokines that could potentiate the cytotoxic action of certain chemotherapeutic agents when administered simultaneously with induction therapy. Such cytokines included granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interleukin 3, and stem cell factor. Phase I and II ...

Notch signaling has been shown to play a key role in cell fate decisions in numerous developmental systems. Using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we reported the expression of human Notch-1 in CD34+ progenitors. In this study, we evaluated the expression of human Notch-1 and Notch-2 protein by ...

Cytotoxicity is an important function of the immune system that results in the destruction of cellular targets by humoral and/or cellular mechanisms. We wanted to assess the possibility of targeting the lytic function of immune cells toward cancer cells, which express the gene coding for a known tumor antigen (Ag) ...

The present study investigates the differences in serum activity of granulocyte-macrophage colony-stimulating factor, macrophage chemoattractant protein-1, and macrophage inflammatory protein-1alpha between hypertensive patients with and without significant hyperlipidemia before receiving any medical treatment. The serum activity of the studied inflammatory factors is more elevated in hypertensive patients with significant hyperlipidemia ...

The effects of the N-linked oligosaccharide inhibitors swainsonine and N-butyldeoxynojirimycin (NB-DNJ) on granulopoiesis was investigated using human bone marrow cells in in vitro liquid and agar cultures. The addition of the inhibitors into cultures containing granulocyte colony-stimulating factor (G-CSF) suppressed maturation from myelocytes into mature neutrophils. Swainsonine did not induce ...

The thrombocytopenia and absent radii (TAR) syndrome is a rare disease associating bilateral radial agenesis and congenital thrombocytopenia. Here, we investigated in vitro megakaryocyte (MK) differentiation and expression of c-mpl in 6 patients. Using blood or marrow CD34(+) cells, the colony-forming unit (CFU)-MK number was markedly reduced. CD34(+) cells were ...

LIGHT was recently described as a member of the tumor necrosis factor (TNF) 'superfamily'. We have isolated a mouse homolog of human LIGHT and investigated its immunoregulatory functions in vitro and in vivo. LIGHT has potent, CD28-independent co-stimulatory activity leading to T-cell growth and secretion of gamma interferon and granulocyte-macrophage ...

Flt3 (fms-like tyrosine kinase 3) ligand (FL) is a potent hematopoietic cytokine that affects the growth and differentiation of progenitor and stem cells both in vivo and in vitro. Its capacity to augment strikingly the numbers of dendritic cells (rare antigen-presenting cells that induce and regulate immune responses) in mice ...

Juvenile myelomonocytic leukemia (JMML) is an early childhood disease for which there is no effective therapy. Therapy with 13-cis retinoic acid or low-dose chemotherapy can induce some responses, but neither mode is curative. Stem cell transplantation can produce lasting remissions but is hampered by high rates of relapse. The pathogenesis ...

Dendritic antigen-presenting cells derived from epidermis (Langerhans cells), bone marrow, and peripheral blood can present a wide variety of antigens, including tumor-associated antigens, for various immune responses. The development and function of dendritic cells is dependent upon a number of cytokines including granulocyte-macrophage-colony-stimulating factor. For example, Langerhans cells can present ...

Only a few cytokines have been tested for their possible role in modulating vascular function. Moreover, no direct effect of cytokines on vascular tone has yet been thoroughly studied. We therefore examined whether a wide range of well-defined cytokines could directly affect vascular tone in isolated human arterial and venous ...

The effect of expression of an O6-benzylguanine (O6-beG)-resistant mutant (hATPA/GA) of human O6-alkylguanine-DNA alkyltransferase (ATase) on the in vivo toxicity and clastogenicity of the anti-tumour agent N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) to murine bone marrow has been investigated. When compared with control animals, the bipotent granulocyte-macrophage colony-forming (GM-CFC) progenitor population of the hATPA/GA ...

The outcome of total joint arthroplasty is determined by biological events at the bone-implant interface. Macrophages phagocytose implant or wear debris at the interface and release proinflammatory mediators such as interleukins 1 and 6, tumor necrosis factor-alpha, and prostaglandin E2. These mediators are thought to contribute to the resorption of ...

Last years there are some reports about influence of erythron cells and immune system. It especially concerns with immunomodulation effect of cells of erythroid series and main humoral erythropoiesis regulator - erythropoietin. Much is known about the influence of cytokines of lymphoid and macrophagal origin on hemopoiesis, and in particular ...

BACKGROUND: The hyper-IgE syndrome is a primary immunodeficiency characterized by severe recurrent abscesses, pneumonia with pneumatocele formation, and elevated serum IgE. Eosinophilia, neutrophil chemotactic defects, and marked tissue damage are frequently present in this syndrome. OBJECTIVE: To study whether functional changes in cytokines, adhesion molecules, and neutrophils might help explain ...

The erythropoietin receptor (EpoR) is essential for production of red blood cells; a principal function of EpoR is to rescue committed erythroid progenitors from apoptosis. Stat5 is rapidly activated following EpoR stimulation, but its function in erythropoiesis has been unclear since adult Stat5a-/-5b-/- mice have normal steady-state hematocrit. Here we ...

Patients with motor neuron disease (MND) (n =33) free of infection were assessed for symptoms of autoimmunity and evidence of peripheral immune activation. Clinical features of autoimmune disease and antinuclear antibodies were notably absent in all patients. Compared with healthy controls, patients with MND had no significant difference in lymphocyte ...

Neutrophil function defects occur in individuals with Down syndrome (DS). We examined apoptosis of granulocytes (neutrophils and eosinophils) in DS individuals and control healthy subjects. Granulocyte survival was shortened in DS individuals, and the percentage of apoptotic granulocytes from DS during incubation was significantly higher than that from healthy subjects. ...

Therapy with colony-stimulating factors has been extended beyond their use in accelerating myeloid cell recovery to take advantage of their immune function-enhancing properties. Studies in animal models and with human subjects suggest a potential role as adjunctive therapy in infections of non-neutropenic hosts, including those with sepsis. Granulocyte colony-stimulating factor ...

Granulocyte-macrophage colony-stimulating factor is by far the most widely used hematopoietic growth factor to augment immune responses. At present, the best secured effect is as an adjuvant cytokine for vaccination. Granulocyte-macrophage colony-stimulating factor can be delivered as gene-transduced tumor cells, as plasmid DNA, or as the soluble free granulocyte-macrophage colony-stimulating ...

Colony-stimulating factor 1 (CSF-1) is required for the development of monocytes/macrophages from progenitor cells and for the survival and activation of mature macrophages. The receptor for CSF-1 is the product of the c-fms proto-oncogene, which, on binding ligand, can stimulate a mitogenic response in the appropriate cells. To investigate which ...

G proteins play an important role in signal transduction from cytokine receptors to intracellular effectors via different pathways, eg involving tyrosine kinases. In our previous studies, we demonstrated that mRNA expression of the hematopoiesis-specific G protein alpha-subunit G alpha16 is a sensitive marker indicating the appearance of early myeloid and ...

Liposome-encapsulated dichloromethylene diphosphonate (L-MDP) has been used for depleting cells of the monocyte-macrophage lineage. We have undertaken this study to investigate whether dendritic cells are susceptible to this liposome-encapsulated compound. Dendritic cells were cultured in the presence of L-MDP and further processed for apoptosis detection. The highly characteristic DNA cleavage ...

The erythropoietin receptor (EpoR) has been previously shown to contain a cytoplasmic C-terminal negative regulatory domain, experimental deletion or mutation of which leads to increased sensitivity of expressing cells to the effects erythropoietin (Epo). We have studied a naturally occurring C-terminal truncation mutant of the human EpoR by stably transfecting ...

Troglitazone (TGL), a thiazolidinedione compound that improves the response of peripheral target tissue to insulin, also has anti-inflammatory properties, a potential means of protection from Type 1 (insulin dependent) diabetes. In order to test the ability of TGL to affect cytokine production, peripheral blood mononuclear cells from healthy donors were ...

The interference of low-molecular-weight phosphotyrosine protein phosphatase with the macrophage response to macrophage colony-stimulating factor was investigated. This paper shows that this phosphatase, already known to be involved in platelet-derived growth factor receptor signaling, is physiologically expressed in murine macrophages and dephosphorylates in vitro macrophage colony-stimulating factor receptor molecules immunoprecipitated ...

We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic ...

Proinflammatory effects induced by the serine protease factor Xa were investigated in HUVEC. Exposure of cells to factor Xa (5-80 nM) concentration dependently stimulated the production of IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) and the expression of E-selectin, ICAM-1, and VCAM-1, which was accompanied by polymorphonuclear leukocyte adhesion. The ...

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell disorder characterized by complement-mediated hemolysis and deficient hematopoiesis. The development of PNH involves an acquired mutation in the X-linked PIG-A gene, which leads to incomplete bioassembly of glycosylphosphatidylinositol (GPI) anchors and absent or reduced surface expression of GPI-linked proteins. The origin ...

In polycythemia vera (PV) erythroid colonies that grow in vitro in the absence of exogenous erythropoietin (EPO) arise from the abnormal clone that is responsible for overproduction of red blood cells. Although the mechanism of autonomous formation of burst-forming units-erythroid (BFU-E) is not fully understood, a spontaneous release of growth ...

OBJECTIVES: Altered cytokine expression at the fetoplacental interface may be a potential mechanism for the development of fetal immune dysfunction in children with fetal alcohol syndrome. This study was conducted to determine whether first-trimester trophoblasts respond to ethanol exposure by the induction of specific cytokines. STUDY DESIGN: HTR-8/SVneo trophoblast cells ...

Optimal regimens for the treatment of invasive fungal infections have yet to be defined, and these life-threatening conditions are one of the leading causes of treatment failure in patients with cancer. A substantial body of preclinical work points in the direction of using cytokines as immunomodulators of the multiple deficiencies ...

SHIP is a 145-kD SH2-containing inositol-5-phosphatase widely expressed in hemopoietic cells. It was first identified as a tyrosine phosphoprotein associated with Shc in response to numerous cytokines. SHIP has been implicated in FcgammaRIIB receptor-mediated negative signaling in B cells and mast cells and is postulated to down-regulate cytokine signal transduction ...

Historical clinical observations suggested that cellular immunity is central in the outcome of deep fungal infections, and experimental observations later proved this. Unstimulated effector cells interact synergistically with antifungal drugs. Recombinant cytokines, of which interferon gamma (IFN-gamma) is the most prominent, stimulate several host-effector cells (macrophages, monocytes, neutrophils) for antifungal ...

Little is known concerning the interaction of thrombopoietin (TPO) with other megakaryocyte-active cytokines in directing the early events of megakaryocyte development. Culture of CD34(+) cells in interleukins (IL) -1, -6, -11, plus stem cell factor (SCF; S) results in a 10- to 12-fold expansion in total cell numbers, whereas total ...

We investigated how in vivo effects of single hematopoietic cytokines change if given in combination for a prolonged time. Mice were treated with every combination of recombinant human (rh) erythropoietin (EPO), rh granulocyte colony-stimulating factor (G-CSF), recombinant rat (rr) stem cell factor (SCF), and rh interleukin (IL)-11 by continuous infusion ...

The effects of oncostatin M on the expression of different cytochrome P450 (CYP) isozymes has been investigated in human hepatocytes. The dose-response and time-course analyses of effects on CYP1A2 and CYP3A4 isozymes revealed that maximal inhibition was reached after 48 hr of exposure of human hepatocytes to 25 units/ml oncostatin ...

Highly enriched, bipotent, hematopoietic granulocyte macrophage colony-forming cells (GM-CFC) require cytokines for their survival, proliferation, and development. GM-CFC will form neutrophils in the presence of the cytokines stem cell factor and granulocyte colony-stimulating factor, whereas macrophage colony-stimulating factor leads to macrophage formation. Previously, we have shown that the commitment to ...

The fetal liver is the main hematopoietic organ during intrauterine life. Morphometrical studies were performed on liver sections to detect changes occurring with intrauterine growth retardation and preeclampsia. Compared with the controls (n = 10), fetuses from preeclamptic mothers showed a severe reduction of erythroid cells by 60% on average ...

A combination of in vitro and in vivo molecular genetic approaches have provided evidence to suggest that AP-1 (Fos/Jun) transcription factors play multiple roles in functional development of hematopoietic precursor cells into mature blood cells along most, if not all, of the hematopoietic cell lineages. This includes the monocyte/macrophage, granulocyte, ...

Erythropoietin is known to be an essential hemopoietic growth factor for maturation of erythroid progenitor cells. Like other hemopoietic growth factors, erythropoietin acts as a survival factor that supports maturation of the erythroid progenitor through the suppression of apoptosis. It is unclear whether erythropoietin can also induce differentiation, or if ...

Bibliography: leaves 165-193.

Hematopoiesis is the process by which mature, functional progeny of the eight major lineages of blood cells are produced from a hierarchy of progressively less mature progenitor and stem cells. The control of hematopoiesis involves intimate cellular interactions between developing blood cells and stromal elements as well as regulation by ...

Neutropenia is often attributed to immunologically mediated injury to mature neutrophils or their precursors. Clinically it is useful to classify immune mediated neutropenias as isoimmune, autoimmune (including some drug-associated neutropenias), and idiopathic (cases possibly with an immune mechanism). Isoimmune neutropenia occurs in infancy and the antigen and is an isoform ...

To investigate the cytokines involved in the interaction between circulating (B and T lymphocytes) and non-circulating (stromal cells) elements present in lymphoid tissue, highly purified populations were isolated from human tonsils and the cytokine production and mRNA expression (interleukin-1 alpha, -2, -4, -5, -6, -8, -10, leukocyte inhibitory factor, granulocyte-macrophage ...

Systemic fungal infections are an increasingly important threat to immunocompromised patients. In particular, invasive disease due to Candida spp., Aspergillus spp. and other moulds is associated with high mortality rates in these patients, despite the many recent advances in antifungal chemotherapy. Recent studies examining the immunopathogenesis of these infections have ...

In patients with paroxysmal nocturnal hemoglobinuria (PNH), we measured plasma concentrations of endogenous hematopoiesis-regulatory cytokines to characterize bone marrow (BM) hypoplasia which is a major cause of death. Contrary to 10 healthy individuals, all 14 patients with PNH showed increases of erythropoietin (Epo) and granulocyte-colony stimulating factor (G-CSF). There were ...

The response of human peripheral blood mononuclear cells (MNC) to Aspergillus fumigatus in vitro was evaluated. In studies of the proliferative response of MNC from 18 healthy donors to heat-killed A. fumigatus conidia, 15 displayed a significant response, with a stimulation index (SI) between 4 and 193. In contrast, all ...

STUDY DESIGN: Cultures established from murine disc-derived cells were stimulated by lipopolysaccharide. The cells' capacity to secrete proinflammatory cytokines and interleukin-10 with and without lipopolysaccharide stimulation was determined using enzyme-linked immunosorbent assays. OBJECTIVES: To determine the capacity of disc-derived cells to secrete proinflammatory cytokines, and the effect of lipopolysaccharide stimulation ...

Erythropoietin (Epo) is known to control the erythroid developmental program through various biologic activities including maintenance of viability, cell proliferation, and/or cell maturation. In vitro experiments showed massive apoptosis in cultures of Epo-deprived colony-forming unit-erythroid (CFU-E) progenitors, demonstrating the Epo requirement of late-stage erythroid progenitors for survival. Based on these ...