CONTENTS
Review
- CD45 in Memory and Disease
Elma Z. Tchilian and Peter C.L. Beverley (The Edward Jenner Institute for Vaccine Research, Compton, UK)Abstract. CD45 (the leukocyte common antigen) is known to function as a tyrosine phosphatase in leucocyte signalling. Biochemical studies indicate that CD45 is involved in the regulation both of T cell receptor-associated kinases and Janus kinases that transmit signals from cytokine receptors. However the function of the different isoforms of CD45 generated by complex alternative splicing, and indeed the role of the whole extracellular domain of the molecule, remain mysterious. Analysis of CD45 knockouts and of transgenic mice expressing single CD45 isoforms, as well as the disease associations of human polymorphisms, is providing new insights into CD45 function. Accumulating data from these genetic and biochemical studies promises to elucidate the role of high and low molecular weight isoforms of CD45 in the function of naive and memory T lymphocytes.
Keywords: CD45; cellular signaling; memory T lymphocytes.
- Low Molecular Weight Protein Tyrosine Phosphatase and Human Diseases: in Search of Biochemical Mechanisms
Nunzio Bottini, Tomas Mustelin (Program of Signal Transduction, La Jolla Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA), Egidio Bottini (Department of Neurosciences), Fulvia Gloria-Bottini (Department of Biopathology, University of Rome Tor Vergata, Rome, Italy)Abstract. A major challenge in the post-genomic era is to identify the physiological function of genes and elucidate the molecular basis for human disease. Genetic polymorphisms offer a convenient aveune for these efforts by providing evidence for the involvement of a given gene in human pathophysiology. Here we review the current evidence linking the low molecular weight protein tyrosine phosphatase (LMPTP) to several common diseases, including allergy, asthma, obesity, myocardial hypertrophy, and Alzheimer’s disease. Based on the know effects of the genetic polymorphisms on the alternative mRNA splicing and enzyme levels of LMPTP, we discuss the possible molecular mechanisms of LMPTP involvement in these diseases.
Keywords: tyrosine phosphate; genetic polymorphisms; allergy; asthma; obesity.
- Significance of Tumor-Cell Receptors in Human Cancer
Jan Żeromski (Chair and Department of Clinical Immunology, Karol Marcinkowski University of Medical Sciences, Poznań, Poland)Abstract. Every tumor cell is equipped with an array of biologically active surface molecules, and several these function as receptors for various ligands. They include MHC, or in the case of humans, HLA antigens, cytokine receptors, cell-adhesion molecules, growth factor receptors, Fas/Fas-ligand molecules and others. Their expressions are a subject to alterations, usually to the advantage of tumor growth and spread. Some appear on tumor cells de novo, having no counterparts on the respective normal cells. Detailed knowledge about the expression of tumor-cell receptors and their genotypes, in particular of cancerous ones, may provide information essential for the creation of tools for specific tumor immunotherapy.
Keywords: HLA antigens; cytokine receptors; adhesion molecules; growth factors.
- Potential for Immune Reconstitution by G-CSF Treatment in HIV Patients
Sonja von Aulock and Thomas Hartung (Biochemical Pharmacology, University of Konstanz, Konstanz, Germany)Abstract. New treatment strategies for HIV/AIDS are very successful in reducing viral load. However, reconstitution of the immune system takes about one year and may be insufficient or remain incomplete. During this time the patient remains prone to opportunistic infections as a result of the complex immune dysfunction caused by the virus. Recombinant granulocyte colony-stimulating factor (G-CSF) has diverse immunomodulatory properties which may be beneficial to aid immune reconstitution.
Keywords: HIV; AIDS; G-CSF; immune reconstitution.
- GM-CSF Regulation in Eosinophils
Stéphane Esnault and James S. Malter (Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA)Abstract. Allergic asthma is characterized by a temporally and quantitatively inappropriate immunologic response. One of hallmarks of this response is the accumulation of eosinophils in the airway and lung parenchyma, which results in bronco-constriction, lung damage and ultimately fibrosis. GM-CSF plays a pivotal role in this process by modulating eosinophil function and survival. In this review, we discuss the effects and molecular regulation of GM-CSF secretion by eosinophils. Recent data demonstrate activated eosinophils release small amounts of anti-apoptotic GM-CSF by stabilizing its coding mRNA.
Keywords: eosinophils; GM-CSF; mRNA; survival; asthma.
- Immunomodulation of Macrophages by Pathogenic Yersinia Species
Klaus Ruckdeschel (Max von Pettenkofer-Institute for Hygiene and Medical Microbiology Pettenkoferstr. 9a, 80336 Munich, Germany)Abstract. The interaction between macrophages and bacterial pathogens plays a crucial role in the pathogenesis of infectious diseases. Pathogenic species of the gram-negative bacterium Yersinia deploy complex strategies to disarm macrophages and to disrupt their response to infection. For this purpose, Yersinia spp. engage a type III protein secretion system that mediates polarized translocation of Yersinia virulence factors, the so-called Yops, into the host cell cytoplasm. There, the Yops act on different cellular levels to neutralize a sequence of programmed phagocyte effector functions. Yersiniae initially impair the phagocytic machinery and block the generation of the bactericidal oxidative burst. Furthermore, yersiniae uncouple an array of fine-tuned signals of innate immunity, which leads to suppression of the macrophage TNF-a production and to macrophage apoptosis. The impairment of cellular functions results in a scenario, by which Yersinia efficiently resist the attack of the macrophage and finally kills the macrophage by activating its intrinsic cell suicide mechanism. This review highlights the aspects of Yersinia-macrophage interaction that determine the fate of the infected cell.
Keywords: Yersinia; macrophage; apoptosis; YopP/YopJ; NF-kB.
Clinical Immunology
- Effect of IL-18 on IL-lb and sIL-1RII Production by Human Neutrophils
Ewa Jabłońska, Aneta Iżycka and Natalia Wawrusiewicz (Department of Immunology, Medical Academy of Białystok, Poland)Abstract. In the present study we investigated the effect of interleukin-18 (IL-18) on the production of interleukin-1b (IL-1b) and soluble interleukin-1 receptor II (sIL-lRII) by human neutrophils. The results obtained indicate that recombinant human interleukin-18 (rhIL-18) induces IL-lb and, to a lesser extent, sIL-1RII production by human neutrophil isolated from peripheral blood. However, this effect was less important than lipopolysaccharide (LPS) stimulation. Additionally, our observations suggest that IL-18 can induce priming of neutrophils for IL-lb and, to a lesser extent, sIL-lRII production by LPS-stimulated cells. The ability of IL-18 to serve as an effective modulator for IL-lb and its regulatory protein may have significance in the inflammatory and immune reactions mediated by IL-lb.
Keywords: neutrophil, interleukin-18, interleukin-1b, soluble interleukin-1 receptor II.
- A Study of Thyroglobulin Concentration in the Thyroid and Serum of Patients with Different Thyroid Disorders
Agata Czarnywojtek, Iwona Krysińska, Katarzyna Łącka, Maciej Gembicki (Department of Endocrinology, Institute of Internal Medicine, K. Marcinkowski University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznań, Poland), Bolesław Stawny (Department of General and Gastroenterological Surgery, Poznań, Poland), Michał Rólski (Department of Children Surgery, University of Medical Sciences, Poznań, Poland), Jan Włoch (Oncology Centre, M. Skłodowska-Curie Institute, Gliwice, Poland)
Abstract. Knowledge concerning the structure and quality of thyroglobulin (Tg) has great significance for the better understanding of the pathogenesis of different thyroid diseases. The localisation of the Tg gene and studies of its structure by molecular biological techniques make possible precise investigations of its expression. The aim of our study was to evaluate Tg content in the thyroids and Tg concentrations in the serum of 108 patients suffering from benign or malignant thyroid disorders. The method of investigation was isolating total protein from thyroid tissues obtained during surgery and determining Tg content in the thyroid extracts and Tg concentrations in serum. The Tg concentrations in serum and in thyroid protein extracts were evaluated by fluoroimmunometric assay. Statistical analysis was carried out with the help of the computing programmes.
Keywords: thyroglobulin; thyroid disorders; protein extracts.