M Wasik

Medical University of Warsaw, Warsaw, Masovian Voivodeship, Poland

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Publications (104)206.13 Total impact

  • E Gorska, K Popko, M Wasik
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    ABSTRACT: Ob-R receptor is encoded by db gene and belongs to class I cytokine receptors family. Its expression was observed in hematopoietic CD34+ stem cells, erythropoietic, myeloid and lymphoblastic lineages cell lines and in human leukemic blast cells in lymphomas, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML). The studies on human bone marrow cells show that JAK/STAT pathway plays a substantial role in signal transduction in young bone marrow cells. The aim of the study was to examine the relationship between leptin receptor expression and the proliferation of neoplastic hematopoietic cells in bone marrow. The study was performed in a total of 57 children of both sexes aged 3 months to 16 years. A group of 46 patients with acute leukemia involved 25 children with ALLB, 11 children with ALLT and 10 children with ANNL. The control group consisted of 11 non-obese children with non-malignant hematological disturbances. The tests were performed on bone marrow samples. The assessments of membrane expression of Ob-R and the antigens determining the phenotype of bone marrow cells were performed using a flow cytometry method. In acute lymphoblastic leukemia, a significant decrease of Ob-R expression on leukemic blasts was observed in comparison with respective populations of normal bone marrow cells. Also in progenitor cells populations a significant decrease of CD34+Ob-R+w ALLT and ALLB was observed in comparison with the cells from normal bone marrow. No statistically significant differences in the percentage of Ob-R+ cells in ANNL bone marrow and in control bone marrow were observed.
    Advances in experimental medicine and biology 01/2013; 756:155-61. · 1.83 Impact Factor
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    ABSTRACT: The cytotoxic T lymphocyte antigen-4 (CTLA-4) (CD152) is a basic negative regulatory molecule of T cell activation and its hypo-function is associated with severe lymphoproliferative syndrome. The aim of the present study was to evaluate the intracellular and surface expression of CTLA-4 on peripheral T cells before and after T cell activation in children with Hashimoto's thyroiditis (HT). Blood samples were obtained from 46 children: 25 with Hashimoto's thyroiditis and 21 controls free of autoimmune disease or thyroid disorders. T cell phenotype was evaluated by flow cytometry with the use of monoclonal antibodies combination: CD4- FITC/ CD28 -PC5/ CD152 -PE and CD8 -FITC/ CD28 -PC5/ CD152 -PE on T cell surface and intracellularly at baseline and after 48 h of T cell culture with the mitogen 48-PHA. We found that the number of T cells with intracellular CD152 expression was comparable in HT patients and controls at baseline and increased after 48-PHA, in CD4 subset only, in both patients and controls. However, the increase was more evident in the HT patients. The number of T cells with the surface expression of CD152 at baseline was significantly lower in the HT patients than in controls (p < 0.0002) in non-stimulated CD4+ and CD8+ T cells. After 48-PHA, surface CD152 expression in CD4+T cells increased in both groups; the increase was greater in controls. In conclusion, impaired function of CTLA-4 in HT patients may depend on the imbalance of intracellular/surface expression of CD152 in T cells.
    Advances in experimental medicine and biology 01/2013; 756:163-8. · 1.83 Impact Factor
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    ABSTRACT: Leptin or obesity receptor (Ob-R) is a member of class I cytokine receptor family. Ob-R, expressed in six isoforms, is the product of alternative RNA splicing of db gene. According to its structural differences, the receptor's isoforms are divided into three classes: long, short, and secretory isoforms. A long, fully active isoform of Ob-Rb is expressed mainly in the hypothalamus, where it takes part in energy homeostasis and in the regulation of secretory organs' activity. Ob-Rb is also present on all types of immune cells, involved in innate and adaptive immunity. Short leptin isoforms (Ob-Ra, Ob-Rc, Ob-Rd, and Ob-Re) that contain box 1 motif are able to bind JAK kinases (Janus kinases) as well as to activate some other signal transduction cascades. A soluble isoform (Ob-Re) can regulate serum leptin concentration and serve as a carrier protein delivering the hormone to its membrane receptors and is able to transduce the signal into the cell. JAK/STAT pathway plays the major role in leptin signal transduction through membrane receptors. Among all Ob-R isoforms, only full-length isoform (Ob-Rb) is able to fully transduce activation signal into the cell.
    European journal of medical research 11/2010; 15 Suppl 2:50-4. · 1.10 Impact Factor
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    ABSTRACT: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is one of the basic antigens involved in immune responses regulation associated with autoimmune thyroid diseases. The aim of the study was to evaluate whether the surface expression of CTLA-4(CD152) on T cells is correlated with laboratory autoimmune markers in children with Hashimoto's disease. Blood samples were obtained from 45 children with Hashimoto's thyroiditis of the mean age 14.8 ±2.35 years, and from 55 healthy age-matched children, free of allergic, immune and hematological disorders, and with a normal thyroid function. The anti-thyroid antibodies were measured with Microparticle Enzyme Immunoassay (AxSYM Anti-Tg, AxSYM Anti-TPO). The T cell phenotype was evaluated flow cytometery, with the use of monoclonal antibodies combination: CD4- FITC/ CD28 -PC5/ CD152 -PE and CD8 -FITC/ CD28 -PC5/ CD152 -PE. - The percentage of T cells with CD152 expression was significantly decreased in children with Hashimoto's thyroiditis compared with healthy controls (P<0.001). A significant negative correlation was found between the level of anti-thyroglobulin antibodies and the percentage of CD4+CD152+ T cells (r = -0.34; P<0.05). Anti-thyroperoxidase antibodies did not correlate with CD152 expression. In children with Hashimoto's thyroiditis, the number of CD4+CD152+ T cells is decreased and negatively correlates with the level of anti-thyroglobulin antibodies.
    European journal of medical research 11/2010; 15 Suppl 2:72-5. · 1.10 Impact Factor
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    ABSTRACT: The resistance of T lymphocytes to Fas-mediated apoptosis is an important feature of atopic asthma. The only effective causative treatment of atopic diseases is immunotherapy. Clinical efficacy of sublingual immunotherapy (SLIT) has been already proven, but there is still limited number of studies on its influence on lymphocytes function. The aim of the study was to evaluate whether SLIT could restore the sensitivity of asthmatic T cells to undergo Fas-mediated apoptosis. Peripheral blood was collected from 12 patients aged 8 ±2 years suffering from atopic asthma and undergoing sublingual specific immunotherapy. To evaluate sensitivity to Fas-mediated apoptosis, the blood was transmitted to sterile tubes and mixed with purified monoclonal antibody anti-CD95. After incubation, leukocytes were stained with Annexin V, propidium iodide, and monoclonal antibody against CD2 conjugated with phycoerythrin-cyanin 5.1, and then analyzed with flow cytometry. The procedure was repeated for each patient after 12 months of SLIT. - Results: Stimulation with anti-CD95 of T lymphocytes from patients with atopic asthma before treatment increased the number of early apoptotic cells (from 19.5 ±16.7% before stimulation to 26.6 ±16.7% Annexin V positive cells after stimulation). After one year of SLIT anti-CD95 still caused an increase of the early apoptotic cells ratio in the lymphocyte population (from 12.4 ±7.4% before stimulation to 24.7 ±15.4% Annexin V positive T cells after CD95 stimulation). Although an increasing trend could be observed, differences between the analyzed groups were not statistically significant. A year of SLIT does not change the sensitivity of T lymphocytes from peripheral blood of children suffering from atopic asthma to Fas-mediated apoptosis.
    European journal of medical research 11/2010; 15 Suppl 2:17-20. · 1.10 Impact Factor
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    ABSTRACT: The aim of the study was to investigate whether the Gln223Arg in the leptin receptor may influence body weight, leptin concentration, and metabolic parameters in children. The examined group included 101 obese children (58 girls and 43 boys) with BMI 31.41 +/-5.03 kg/m(2) (BMI > or = 2 SDS) and the control group consisted of 41 children with BMI 20.0 +/-0.80 kg/m2 (BMI <1.0 SDS). Polymorphism identification was performed in total genomic DNA using PCR-RFLP method. The distribution of genotypes LEPR was the following: in the obese group: AA - 20.8%, AG- 55.4%, GG-23.8 %; in the control group AA-31.7%, AG- 53.65%, GG-14.65%. Comparative analyses between AA homozygous children and carriers of G alleles did not confirm any relation between the analyzed polymorphism and BMI, leptin concentrations, and metabolic disturbances in children with obesity. In children with obesity we did not observe association of the LEPR Gln223Arg gene polymorphism with obesity, leptin, insulin resistance, and metabolic abnormalities.
    European journal of medical research 12/2009; 14 Suppl 4:201-4. · 1.10 Impact Factor
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    ABSTRACT: The aim of the study was to investigate whether the G-174C polymorphism of the IL-6 gene is related to obesity and the incidence of the metabolic syndrome (MetS) according to IDF definition in children. The examined group included 124 obese children with BMI > or = 2 SDS, and the control group consisted of 56 non-obese children with BMI <1.0 SDS. Polymorphism identification was performed in total genomic DNA using PCR-RFLP method. In the obese children, carriers of C allele in homozygotic and heterozygotic genotypes were more frequent than in the control group. The carriers of C alleles presented with lower thickness of subcutaneous tissue and higher concentrations of HDL-C than the wild type. The incidence of MetS was 33% of the group of obese children. Analysis of the presence of MetS factors showed that there is more frequent MetS in the group with the wild homozygous genotype type. Polymorphism 174G>C in the IL-6 gene does not seem to be associated with obesity and with the incidence of MetS in children.
    European journal of medical research 12/2009; 14 Suppl 4:196-200. · 1.10 Impact Factor
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    ABSTRACT: Obesity development is a complex process which can be influenced by genetic predisposition modified by environmental factors. Nowadays, the problem of overweight and obesity, including related complications, occurs in increasingly younger children. Thus, there is a need for new genetic markers of increased risk of excessive body mass. The aim of the present study was to examine the relation between polymorphisms located in promoter regions of IL-1beta, IL-6, and TNF-alpha genes and obesity development in children. Fifty obese and 55 normal weighing children were enrolled into the study. Genetic examination was performed using PCR-RFLP technique. We found a relation between G174C polymorphism in IL-6 gene and G308A in TNF-alpha gene with the occurrence of obesity. Allele A in G308A was more frequent in the obese group than in the control one (P=0.04). The presence of allele C in promoter region of IL-6 gene was more frequent in obese children and connected with a statistically significant increase in the sum of 10 skin fold thickness measurements (P=0.03). The polymorphism C3954T in IL-1beta gene showed no such relation. The examined polymorphisms of proinflammatory cytokines play a role in the regulation of body mass through their influence on metabolism and energetic homeostasis.
    European journal of medical research 12/2009; 14 Suppl 4:59-62. · 1.10 Impact Factor
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    ABSTRACT: CTLA-4 gene is one of the strongest locus of genetic susceptibility to autoimmune thyroid diseases. The aim of the present study was to investigate surface expression of CTLA-4 on peripheral T cells in homozygotes AA and GG at position +49 of CTLA-4 gene in children with Hashimoto's thyroiditis and in healthy controls. Blood samples were obtained from 100 children: 45 with Hashimoto's thyroiditis and 55 controls. CTLA-4 exon 1 polymorphism was defined by SSCP and RFLP with BbvI enzyme. T cells were analyzed with three color flow cytometry by Coulter EPICS XL. We found that CTLA-4 expression was significantly lower in the thyroiditis patients than in controls, but CTLA-4 expression in homozygotes GG and AA was comparable. We therefore conclude that decreased expression of CTLA-4 on T cells in children with Hashimoto's thyroiditis is not dependent on polymorphic changes at position +49 of CTLA-4 gene.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 11/2009; 60 Suppl 5:77-80. · 2.48 Impact Factor
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    ABSTRACT: The goal of the study was to evaluate the process of Ca(2+)-mediated transduction of signals into neutrophils from patients with type I diabetes and its modification by insulin. The study was performed with the use of isolated peripheral blood neutrophils from 20 diabetic patients and 30 healthy volunteers. Isolated granulocytes were stimulated separately by fMLP or insulin, or by both substances added to the medium in combinations: fMLP + insulin (after 20 min) or insulin + fMLP (after 20 min). fMLP evoked fast intracellular increase of free Ca(2+) concentration in neutrophils compared with the resting state (P<0.001). Similarly, the peak of fluorescence, as measured by Fluo 3 to Fura Red ratio, was significantly higher in neutrophils stimulated by insulin. Insulin did not cause any changes in intracellular Ca(2+) level when it was added to the previously fMLP-stimulated cells. Prestimulation with insulin significantly decreased fMLP-induced intracellular free Ca(2+) concentration, expressed as Fluo3/Fura Red ratio compared with fMLP alone (1.77 +/- 0.6 vs. 2.63 +/- 0.8, P<0.001). No relation between initial intracellular Ca(2+) in the resting state and the response to insulin was found. Nor was the response to fMLP alone related to intracellular Ca(2+) before stimulation. A strong correlation was observed between initial intracellular Ca(2+) after incubation with insulin and the response to fMLP (r=0.90, P<0.0001). In diabetic granulocytes, the intracellular Ca(2+) was significantly lower than in those from healthy donors in unstimulated cells (P<0.001), after fMLP stimulation (P<0.0001), in medium enriched by insulin (P<0.05), and after fMLP stimulation in insulin rich medium (P<0.001). Only in fMLP prestimulated samples, the emission of light did not differ after stimulation with insulin in granulocytes from both diabetic and healthy subjects. In conclusion, patients with type I diabetes have decreased levels of cytosolic Ca(2+) after insulin and fMLP stimulation in polymorphonuclear granulocytes. This abnormality is probably primarily responsible for the impaired neutrophilic function seen in these patients.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 11/2009; 60 Suppl 5:37-40. · 2.48 Impact Factor
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    ABSTRACT: 'Gold standard' in the diagnosis of atopic disease are skin prick tests and specific IgE evaluation. Well-established in vitro tests, such as the histamine release test, the leukotriens release test and the flow cytometric basophil activation test can be very helpful in diagnostics, especially when the skin prick test is contraindicated. The aim of this study was to evaluate the usefulness of antigen CD203c expression, as a marker of basophil activation by grass pollen or D. pteronyssinus antigens. MATERIAL AND METHOds: Peripheral blood from 13 allergic patients and nine healthy volunteers was analysed. Basophils activation was measured by the breakdown of antigen CD203c expression with Allergenicity Kit (Beckman Coulter), using Cytomics FC 500 flow cytometer (Beckman Coulter). The sensitivity was 92.3% and specificity of test was 100%. 50.95 +/- 15.7% of basophils (median 49.7%, 1.91-72.42%) were activated after grass pollen stimulation in atopic patients sensitised to this allergen, in comparison to 1.91% (0.00-7.96%) in control patients (p = 0.002). The percentage of activated basophils after D. pteronyssinus antigens stimulation was 40.6 +/- 25.2% in allergic patients, compared to only 2.51 +/- 1 96% of basophils from non-atopic controls (p = 0.0003). Basophils from 21 patients responded after anti-IgE stimulation (44.1 +/- 18.9%), and none of the analysed samples was activated after PBS stimulation (2.03 +/- 1.19%, p < 0.0001). These results demonstrate that basophil activation test based on antigen CD203c expression is very accurate in the diagnosis of atopic diseases.
    Pneumonologia i alergologia polska: organ Polskiego Towarzystwa Ftyzjopneumonologicznego, Polskiego Towarzystwa Alergologicznego, i Instytutu Gruzlicy i Chorob Pluc 02/2009; 77(2):138-44.
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    ABSTRACT: For several years the incidences of allergic diseases and anaphylactic reactions have been increasing dramatically. Classical method of allergy diagnosis - skin prick test in some situations can provoke life-threatening reactions. Detection of allergen-induced basophil activation by flow cytometry has been shown to be a useful tool for allergy diagnosis in those patients. CD 63 and CD203c have recently been demonstrated as a specific activation markers of basophils that are rapidly up-regulated after allergen challenge in sensitized patients. Although flow-cytometry methods are quite sophisticated and expensive, it could be a good alternative in patients at risk of severe anaphylactic reactions or with contradictory test results.
    Pneumonologia i alergologia polska: organ Polskiego Towarzystwa Ftyzjopneumonologicznego, Polskiego Towarzystwa Alergologicznego, i Instytutu Gruzlicy i Chorob Pluc 02/2009; 77(2):152-8.
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    ABSTRACT: Leptin, also called the satiation hormone plays a key role in regulating body weight, energy intake, and expenditure. Leptin interacts with its receptors, mainly located in the hypothalamus. Moreover, there has been an increasing evidence that leptin exerts pleiotropic effects. Multiple peripheral effects of leptin have been recently described including synthesis of the various hormones, e.g., sexual hormones, thyroid hormones, and growth hormone, as well as regulation of blood pressure, reproduction, osteogenesis, hematopoesis, angiogenesis. Leptin also plays a regulatory function in immunity.and in the process of tumorigenesis. Despite intensive investigations since leptin discovery in 1994 we have much to learn about the leptin mechanism of actions and effects.
    Pediatric endocrinology, diabetes, and metabolism. 02/2009; 15(1):45-50.
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    ABSTRACT: Obesity is one of the most commonly identified factors for the obstructive sleep apnea syndrome (OSAS). Adipose tissue is the source of many cytokines, among them there are IL-6, IL-1, and TNF-alpha. The level of inflammatory cytokines increases in people with OSAS and obesity. The aim of this study was to evaluate the distribution of genotypes in inflammatory cytokine genes in people with obesity-related OSAS. The examined group consisted of 102 person with obesity related-OSAS and 77 normal weight person without OSAS. Genotyping of DNA sequence variation was carried out by restriction enzyme (IL-1: Taq I, IL-6: Lwe I, TNF-alpha: Nco I) analysis of PCR amplified DNA. The study revealed a significant correlation between polymorphism located in the promoter region of inflammatory cytokine genes and obesity-related OSAS.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 01/2009; 59 Suppl 6:607-14. · 2.48 Impact Factor
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    ABSTRACT: The T cell hypothesis of asthma is based on the concept that the disease is driven and maintained by the persistence of a specialized subset of chronically activated T memory cells sensitized against an array of allergenic, occupational or viral antigens. Overreaction of CD4+ T cells in the peripheral blood and airway tissues is an invariant feature of asthma; therefore a potent mechanism for augmenting the number of activated T cells in this disease would be the resistance to the normally programmed pathway for cell death. The aim of the study was to evaluate the presence of apoptotic markers on peripheral blood lymphocytes from healthy and asthmatic children before and after stimulation with antiCD95 antibodies. The blood was collected from 21 children with atopic asthma suffering from allergic rhinitis because of house dust mite and/or grass pollen allergens and 8 healthy children matched for their age and sex. Blood was mixed with purified monoclonal antibody antiCD95 (Beckman Coulter), incubated for 24 hours and than stained with Annexin V andPI (Becton Dickinson). Prepared suspensions were analyzed with Cytomics FC 500 (Beckman Coulter) flow cytometer. Annexin V(+)/PI(-) cells were characterized as early apoptotic, Annexin V(+)/PI(+) as late apoptotic and Annexin V(-)/PI(+) as dead. In unstimulated sample from asthmatic children 21.09+/-11.20% cells were characterized as Annexin V positive/PI negative. After stimulation with antiCD95 Annexin V positive/PI negative cells constituted 18.72+/-9.42% of cells, p=0.1. In unstimulated sample from healthy children 11.69+/-6.70% cells were characterized as Annexin V positive/PI negative. In the sample stimulated with antiCD95 16.54+/-2.98% of cells were Annexin V positive/PI negative, p=0.02. There were no differences between results of late apoptotic and necrotic lymphocytes from healthy and asthmatic children. Performed research indicates that lymphocytes from asthmatic children are resistant to Fas mediated apoptosis.
    Folia Histochemica et Cytobiologica 01/2009; 47(4):647-51. · 1.10 Impact Factor
  • Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 01/2009; 60:37-40. · 2.48 Impact Factor
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    ABSTRACT: The goal of the study was to evaluate the process of neutrophil activation via Ca(2+)-mediated transduction signal and its modification by insulin. The study was performed with the use of isolated peripheral blood neutrophils obtained from 20 healthy volunteers. Isolated granulocytes were stimulated by fMLP or insulin alone, or by both substances added to the medium in combinations: fMLP + insulin (after 20 min) or insulin + fMLP (after 20 min). To explore the mechanism of intracellular Ca(2+) changes, receptor signal transduction pathway was blocked by tyrosine kinase inhibitors: tyrphostin 25 and genistein. fMLP evoked fast intracellular increase of free Ca(2+) concentration in neutrophils, compared with the resting state (P< 0.001). Insulin did not cause any changes in intracellular Ca(2+) when was added to the previously fMLP stimulated cells. Prestimulation with insulin significantly decreased fMLP-induced intracellular free Ca(2+) concentration compared with fMLP alone (P<0.01). A strong correlation was observed between initial intracellular Ca(2+) concentration after incubation with insulin and the response to fMLP (P<0.0001). The tyrphostin 25 did not influence the Ca(2+) concentration in control granulocytes, but inhibited the fMLP-induced intracellular Ca(2+) increase when added before fMLP (P<0.05). In a Ca(2+)-free medium, a strong relationship between intracellular Ca(2+) and the response to fMLP after incubation with tyrphostin was found (P<0.001) The genistein did not influence the intracellular Ca(2+) in non-stimulated cells. However, it inhibited the fMLP-induced Ca(2+) increase when added before fMLP (P<0.05). The genistein added to the suspension of cells after fMLP stimulation did not influence intracellular Ca(2+) level. A positive correlation was found between the initial intracellular Ca(2+) and the response to fMLP of genistein preincubated cells. This effect was seen in both Ca(2+)-rich, and Ca(2+)-free medium We conclude that insulin is a potent immunomodulator and its signaling pathways are mediated by Ca(2+) concentration changes. The process of intracellular Ca(2+) changes following insulin signaling is, at least partly, tyrosine kinase-related. Derangements in the concentration of intracellular Ca(2+) may represent a link between the mechanisms of insulin resistance in diabetes.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 12/2008; 59 Suppl 6:219-29. · 2.48 Impact Factor
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    ABSTRACT: CTLA-4 and CD28+ are regulators of T cell activation. The CTLA-4 gene is associated with variety of autoimmune diseases. The aim of the study was to evaluate changes in basic T cell subpopulations, and the expression of CD152+ and CD28+ before and after T cell stimulation in children with autoimmune thyroiditis (AT), as compared with control subjects. Blood samples were obtained from 35 AT children and 25 healthy children. CD markers were evaluated by flow cytometry at baseline, after the culture with phytohemagglutinin and without stimulation. At baseline, CD152+ expression was lower in patients than in controls (P<10(-6)). After stimulation, there were an increase in CD152+ T cells and decreases in CD28+ and CD4+ cells in controls (P<0.01). In AT children, CD152+ T cells remained stable. CD4+CD152+ T cells correlated inversely with antithyroglobulin antibodies. We conclude that alterations in lymphocyte markers are associated with AT. Stimulation leads to differing changes in T-lymphocyte subsets in both examined children populations.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 12/2008; 59 Suppl 6:375-82. · 2.48 Impact Factor
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    ABSTRACT: Rituximab is used in the treatment of CD20+ B cell lymphomas and other B cell lymphoproliferative disorders. Its clinical efficacy might be further improved by combinations with other drugs such as statins that inhibit cholesterol synthesis and show promising antilymphoma effects. The objective of this study was to evaluate the influence of statins on rituximab-induced killing of B cell lymphomas. Complement-dependent cytotoxicity (CDC) was assessed by MTT and Alamar blue assays as well as trypan blue staining, and antibody-dependent cellular cytotoxicity (ADCC) was assessed by a 51Cr release assay. Statins were found to significantly decrease rituximab-mediated CDC and ADCC of B cell lymphoma cells. Incubation of B cell lymphoma cells with statins decreased CD20 immunostaining in flow cytometry studies but did not affect total cellular levels of CD20 as measured with RT-PCR and Western blotting. Similar effects are exerted by other cholesterol-depleting agents (methyl-beta-cyclodextrin and berberine), but not filipin III, indicating that the presence of plasma membrane cholesterol and not lipid rafts is required for rituximab-mediated CDC. Immunofluorescence microscopy using double staining with monoclonal antibodies (mAbs) directed against a conformational epitope and a linear cytoplasmic epitope revealed that CD20 is present in the plasma membrane in comparable amounts in control and statin-treated cells. Atomic force microscopy and limited proteolysis indicated that statins, through cholesterol depletion, induce conformational changes in CD20 that result in impaired binding of anti-CD20 mAb. An in vivo reduction of cholesterol induced by short-term treatment of five patients with hypercholesterolemia with atorvastatin resulted in reduced anti-CD20 binding to freshly isolated B cells. Statins were shown to interfere with both detection of CD20 and antilymphoma activity of rituximab. These studies have significant clinical implications, as impaired binding of mAbs to conformational epitopes of CD20 elicited by statins could delay diagnosis, postpone effective treatment, or impair anti-lymphoma activity of rituximab.
    PLoS Medicine 04/2008; 5(3):e64. · 15.25 Impact Factor
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    ABSTRACT: To evaluate serum levels of fractalkine (FKN), a mediator of leukocyte transmigration, C-reactive protein (CRP) and expression of integrins CD11a and CD49d on peripheral blood lymphocytes in systemic sclerosis (SSc) and to investigate whether they are modulated by intravenous prostaglandin E1 (PGE1). Serum levels of fractalkine and C-reactive protein and expression of CD11a and CD49d on peripheral blood lymphocytes were assessed in 50 SSc patients and in 18 healthy controls. In 25 SSc patients studied parameters were evaluated also after 3 consecutive daily PGE1 infusions (20 microg-40 microg-60 microg) and after 4 weeks. In SSc fractalkine basal level was significantly higher than in controls (9.04+/-1.79 ng/ml vs. 1.17+/-0.1 ng/ml; p<0.0001) and decreased significantly after PGE1 (5.16+/-1.27 ng/ml, p<0.05). After four weeks fractalkine level was still significantly lower than baseline 7.70+/-2.19 ng/ml (p<0.05). Basal percentage of CD11a (+) nor CD49d (+) lymphocytes in SSc (82.38+/-1.60%, 70.74+/-1.68%, respectively) did not differ from controls (85.73+/-2.04%, 75.62+/-2.48%; respectively, p>0.05). PGE1 treatment resulted in decrease of both CD11a (+) (67.72+/-3.34%, p<0.0001) and CD49d (+) lymphocytes (65.32+/-1.62%, p<0.0001). After 4 weeks the percentage of CD11a (+) and CD49d (+) lymphocytes remained significantly lower than at baseline (77.80+/-2.47% and 65.32+/-1.62%, respectively, both p<0.001). In SSc CRP basal level was significantly higher than in controls (4.70+/-2.01 mg/dl vs. 1.40+/-1.79 mg/dl, p<0.005) and reduced significantly after PGE1 (3.39+/-2.06 mg/dl, p<0.05). After 4 weeks, CRP level (4.38+/-2.19 ng/ml) was significantly lower than baseline (p<0.05). Fractalkine may play an important role in the pathogenesis of vascular dysfunction in systemic sclerosis. Prostaglandin E1 down-regulates serum fractalkine level, as well as CD11a and CD49d expression on peripheral blood lymphocytes, which suggests additional mechanisms in which this vasodilatatory agent exerts its efficacy in systemic sclerosis.
    Clinical and experimental rheumatology 01/2008; 26(4):527-33. · 2.66 Impact Factor

Publication Stats

419 Citations
206.13 Total Impact Points

Institutions

  • 1997–2013
    • Medical University of Warsaw
      • • Zakład Diagnostyki Laboratoryjnej i Immunologii Klinicznej Wieku Rozwojowego
      • • Department of Pediatrics, Hematology and Oncology
      Warsaw, Masovian Voivodeship, Poland
  • 2003
    • Samodzielny Publiczny Dzieci cy Szpital Klinicznyw Warszawie
      Poland
  • 2001
    • Jagiellonian University
      • Medical College
      Kraków, Lesser Poland Voivodeship, Poland
  • 1989
    • Medical University of Lublin
      Lyublin, Lublin Voivodeship, Poland