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Human Leucocytes (human + leucocyte)

Distribution by Scientific Domains

Medical Sciences	87%

Terms modified by Human Leucocytes

human leucocyte antigen

Selected Abstracts

Melatonin Counteracts Alterations in Oxidative Metabolism and Cell Viability Induced by Intracellular Calcium Overload in Human Leucocytes: Changes with Age

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2010
Javier Espino
In fact, the free radical theory of ageing proposes that deleterious actions of free radicals are responsible for the functional deterioration associated with ageing. Moreover, a close relationship exists between calcium homeostasis and oxidative stress. The current work was aimed at proving that intracellular calcium overload induced by N -formyl-methionyl-leucyl-phenylalanine (FMLP) and/or thapsigargin leads to oxidative stress. We additionally examined the effect of melatonin on the levels of reactive oxygen species (ROS) and cell viability in human leucocytes collected from young (20,30-year-old) and elderly (65,75-year-old) individuals under both basal and oxidative stress-induced conditions. Treatments with 10 nM FMLP and/or 1 ,M thapsigargin induced a transient increase in cytosolic free-calcium concentration ([Ca2 + ]c) in human leucocytes due to calcium release from internal stores, and led in turn to oxidative stress, as assessed by intracellular ROS measurement. Non-treated leucocytes from aged individuals exhibited higher ROS levels and lower rates of cell survival when compared to leucocytes from young individuals. Similar results were obtained in FMLP and/or thapsigargin-treated leucocytes from elderly individuals when compared to those from the young individuals. Melatonin treatment significantly reduced both hydrogen peroxide (H2O2) and superoxide anion levels, likely due to its free-radical scavenging properties, and enhanced leucocyte viability in both age groups. Therefore, melatonin may be a useful tool for the treatment of disease states and processes where an excessive production of oxidative damage occurs. [source]

Association of autoimmune disease-related gene polymorphisms with chronic graft-versus-host disease

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2007
Masako Shimada
Summary Chronic graft-versus-host disease (GVHD) is the most common cause of poor outcomes after haematopoietic stem cell transplantation (HSCT), while the pathophysiology of chronic GVHD remains poorly understood. As both chronic GVHD and autoimmune disease share clinical features, we speculated that autoimmune disease-related genes might be candidate chronic GVHD-related genes. Recent large-scale cohort studies showed that Fc receptor-like 3 gene (FCRL3) single nucleotide polymorphism (SNP) and peptidylarginine deiminases citrullinating enzymes 4 gene (PADI4) haplotype were associated with autoimmune disease. The present study investigated the association between polymorphisms of these two genes and the incidence of chronic GVHD. We analysed 123 cases of Japanese human leucocyte antigen-matched sibling recipients and their donors who underwent HSCT. Although PADI4, which is the rheumatoid arthritis-specific related gene, was not associated with the occurrence of chronic GVHD, the recipient FCRL3 -169C/C genotype was significantly less frequent in chronic GVHD patients than in those without chronic GVHD (P = 0·0086). There was no relationship between FCRL3 polymorphism and acute GVHD. As FCRL3 is expressed by B cells and might have an important role in immunoregulation, this significant protective genetic effect raises the question of whether FCRL3 might also be involved in the pathogenesis of chronic GVHD. [source]

Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation from HLA-matched related donors in patients with Fanconi anaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2005
J. Zanis-Neto
Summary Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen-matched related donors. Methotrexate and cyclosporine were given for graft- versus -host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2,3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0·001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44,58) months and 16 (3,52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients. [source]

Retroviral transduction of acute myeloid leukaemia-derived dendritic cells with OX40 ligand augments their antigen presenting activity

BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2004
Soshi Yanagita
Summary Recent studies have shown that human myeloid leukaemia cells can differentiate into dendritic cell (DC)-like cells (leukaemia-DCs) when cultured with a combination of cytokines. In the present study, we examined whether the transduction of leukaemia-DCs with OX40 ligand (OX40L), a member of the tumour necrosis factor (TNF) family, resulted in augmentation of their antigen presenting activity. Bicistronic retroviral vectors expressing both human OX40L and enhanced green fluorescent protein (EGFP) or EGFP alone were generated and used for transduction. Fresh leukaemic cells from five patients with acute myeloid leukaemia (AML) were isolated and retrovirally transduced with OX40L during the culture with a combination of cytokines from stem cell factor, fms -like tyrosine kinase (Flt)-3 ligand, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and TNF- ,. After 7 d, the majority of cells showed DC-like morphology, and expressed higher levels of CD80, CD86 and HLA-DR than fresh leukaemic cells. The transduction efficiency was 8·5,27·2%. Leukaemia-DCs transduced with OX40L elicited higher proliferative response of allogeneic CD4+ T cells than fresh leukaemic cells, non-transduced, or mock-transduced leukaemia-DCs. Co-culture of allogeneic CD4+ T cells with OX40L-transduced leukaemia-DCs was superior in the generation of interferon (IFN)- , producing CD4+ T cells and in production of IFN- ,. Furthermore, OX40L-transduced leukaemia-DCs could elicit significant proliferative response of human leucocyte antigen-matched T cells from the donor in allogeneic stem cell transplantation. These results indicate that retroviral transduction of leukaemia-DCs with OX40L augments their antigen presenting cell activity and thus renders them more suitable for tumour vaccines or ex vivo stimulation of leukaemia-specific T cells. [source]

Dihomo-,-linolenic acid inhibits tumour necrosis factor-, production by human leucocytes independently of cyclooxygenase activity

IMMUNOLOGY, Issue 3 2003
Maaike M. B. W. Dooper
Summary Dietary oils (such as borage oil), which are rich in ,-linolenic acid (GLA), have been shown to be beneficial under inflammatory conditions. Dihomo-GLA (DGLA) is synthesized directly from GLA and forms a substrate for cyclooxygenase (COX) enzymes, resulting in the synthesis of lipid mediators (eicosanoids). In the present study, the immunomodulatory effects of DGLA were investigated and compared with those of other relevant fatty acids. Freshly isolated human peripheral blood mononuclear cells (PBMC) were cultured in fatty acid (100 µm)-enriched medium for 48 hr. Subsequently, cells were stimulated with lipopolysaccharide (LPS) for 20 hr and the cytokine levels were measured, in supernatants, by enzyme-linked immunosorbent assay (ELISA). Phospholipids were analysed by gas chromatography. Fatty acids were readily taken up, metabolized and incorporated into cellular phospholipids. Compared with the other fatty acids tested, DGLA exerted pronounced modulatory effects on cytokine production. Tumour necrosis factor-, (TNF-,) and interleukin (IL)-10 levels were reduced to 60% of control levels, whereas IL-6 levels were not affected by DGLA. Kinetic studies showed that peak levels of TNF-,, occurring early after LPS addition, were inhibited strongly, whereas IL-10 levels were not affected until 15 hr after stimulation. Both the reduction of cytokine levels and the decrease in arachidonic acid levels in these cells, induced by DGLA, were dose dependent, suggesting a shift in eicosanoid-subtype synthesis. However, although some DGLA-derived eicosanoids similarly reduced TNF-, levels, the effects of DGLA were probably not mediated by COX products, as the addition of indomethacin did not alter the effects of DGLA. In conclusion, these results suggest that DGLA affects cytokine production by human PBMC independently of COX activation. [source]

Intervention with polyphenol-rich fruit juices results in an elevation of glutathione S -transferase P1 (hGSTP1) protein expression in human leucocytes of healthy volunteers

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 12 2006
Thomas Hofmann
Abstract Polyphenols are probably antigenotoxic on account of their antioxidant activities and might alter phase I and II enzymes in a way that results in chemoprotection. We investigated the hypothesis that polyphenols enhance expression of glutathione S -transferases (GSTs), which increases carcinogen detoxification and thereby provides protection against oxidative stress. HGSTP1 protein expression and GST polymorphisms were determined in leucocytes obtained during an intervention study with healthy subjects consuming two fruit juices in an 8 wk trial (polyphenol-free run in phase, juice intervention phase, washout phase, second juice intervention phase, each treatment regime lasted for 2 wk). The study had originally shown that juice intervention significantly reduced oxidative DNA damage in leucocytes at week 8 (Bub, A., Watzl, B., Blockhaus, M., Briviba, K. et al., J. Nutr. Biochem. 2003, 14, 90,98). We reanalysed the levels of DNA damage based on GST genotypes. We also treated leucocytes in vitro with mixtures of polyphenols and determined cytotoxicity and expression of 96 genes related to drug metabolism. Key results with leucocytes of the intervention study were that the initial content of hGSTP1 protein was first suppressed at weeks 4 and 6. At week 8, however, hGSTP1 protein expression was significantly increased. HGSTP1 protein levels and DNA damage were inversely correlated (p = 0.005), but there was no difference for cells obtained from subjects with hGSTM1*1 and hGSTM1*0 genotypes, nor was there any difference between cells from subjects consuming the two different juices. The treatment of leucocytes with polyphenol mixtures in vitro did not result in modulated GST gene expression or total GST activity, but in an up-regulation of other biotransformation enzymes (e. g., members of the cytochrom P450 and the sulphotransferase family). In conclusion, in vitro treatment of leucocytes led to a modulated mRNA expression of selected genes, not directly related to oxidative defence systems. In vivo, however, we observed a delayed enhancement of hGSTP1, which could be associated with an initial repression of oxidative DNA damage in leucocytes from human subjects, consuming juices with high levels of polyphenols. [source]

Melatonin Counteracts Alterations in Oxidative Metabolism and Cell Viability Induced by Intracellular Calcium Overload in Human Leucocytes: Changes with Age

Blockade of superoxide generation prevents high-affinity immunoglobulin E receptor-mediated release of allergic mediators by rat mast cell line and human basophils

CLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2002
T. Yoshimaru
Summary Background Previous studies have shown that rat peritoneal mast cells and mast cell model rat basophilic leukaemia (RBL-2H3) cells generate intracellular reactive oxygen species (ROS) in response to antigen challenge. However, the physiological significance of the burst of ROS is poorly understood. Objective The present study was undertaken to investigate the role of superoxide anion in mediator release in rat and human cell systems. Methods RBL-2H3 cells were directly stimulated with anti-rat Fc,RI ,-subunit monoclonal antibody (mAb). For the analysis of human cell system, leucocytes were isolated by dextran sedimentation from healthy volunteers or from patients, and challenged either with anti-human Fc,RI mAb or with the relevant antigens. Superoxide generation was determined by chemiluminescence-based methods. The releases of histamine and leukotrienes (LT)s were determined by enzyme-linked immunosorben assay (ELISA). Results Cross-linking of Fc,RI on RBL-2H3 cells or on human leucocytes from healthy donors by the anti-Fc,RI mAb resulted in a rapid generation of superoxide anion, as determined by chemiluminescence using superoxide-specific probes. Similarly, leucocytes from patients generated superoxide anion in response to the challenge with the relevant allergen but not with the irrelevant allergen. Furthermore, diphenyleneiodonium (DPI), a well-known inhibitor of flavoenzymes suppressed the superoxide generation and the release of histamine and LTC4 induced by the anti-Fc,RI mAb or by allergen in parallel. Conclusion These results indicate that both RBL-2H3 cells and human basophils generate superoxide anion upon Fc,RI cross-linking either by antibody or by allergen challenge and that blockade of the generation prevents the release of allergic mediators. The findings strongly support the role of superoxide generation in the activation of mast cells and basophils under both physiological and pathological conditions. The findings suggest that drugs regulating the superoxide generation have potential therapeutic use for allergic disorders. [source]