CONTENTS
Review
- The Role of Hepatocyte Growth Factor/c-met Interactions in the Immune System
Grzegorz Skibinski (Respiratory Research Group, Department of Clinical Biochemistry, Institute of Clinical Science, Queen’s University of Belfast, Belfast BT12 6BJ, Northern Ireland, UK)Abstract. Hepatocyte growth factor (HGF) is a pleiotropic cytokine with mitogenic, motogenic and morphogenic activity for mainly epithelial and endothelial target cells. All the different effects of HGF are mediated through its specific receptor met, a heterodimeric transmembrane tyrosine kinase. The broad activity of HGF and its impact on many physiologic and pathologic processes are reflected by met expression in a variety of organs and cell types. This paper discusses expression of HGF and c-met within the immune system and their interactions in the control of immune cell functions.
Keywords: hepatocyte growth factor; c-met; immune system cell functions
- Processes Involved in the Repair of Injured Airway Epithelia
Yohannes Tesfaigzi (Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA)Abstract. Recent studies have uncovered many aspects of the repair processes that follow airway epithelial injury. Although the repair process has common elements among various epithelia, such as the ones lining the airways, skin, and gut, there are differences based on their diverse functions. Whenever possible, similarities are pointed out that could help researchers further investigate their application to airway epithelia, although it would be beyond the scope of this review to cover the processes that may occur during the repair of all types of epithelia. In general, five major steps are involved in the recovery of airway epithelia from injury: 1) epithelial cells migrate to cover denuded areas within minutes, and certain proteins, such as the trefoil factor family proteins, are crucial to this process; 2) epithelial cells start to proliferate in order to replace injured cells and to differentiate to establish squamous or mucous cell metaplasia; 3) because more epithelial cells are present after proliferation, some of the cells must be discarded to restore the epithelium to the original condition; 4) once the cell numbers have been reduced to those found in unexposed individuals, the normal proportions of cell types are restored; 5) finally, studies from exposures of rats to ozone show that epithelial cells can adapt and develop a memory of the chronic exposure to which they were exposed. This adaptation allows the epithelium to respond quickly, thus minimizing further injury. Although the molecular mechanisms involved in these major steps of the recovery process are largely unknown, disruption of these steps clearly causes the permanent changes observed in diseases such as asthma, chronic bronchitis, and cancer; therefore, extensive research in these areas may provide ideas for novel therapies.
Keywords: epithelium, proliferation, cell cycle, apoptosis, differentiation, homeostasis.
- The Immunology of Chlamydia trachomatis
Bożena Zdrodowska-Stefanow (Department of Dermatology and Venerology, Medical University, Białystok, Poland), Iwona Ostaszewska-Puchalska and Katarzyna Puciło (Center for STD Research and Diagnostisc, Białystok, Poland)Abstract. Chlamydia trachomatis (C. tachomatis) is one of the most common sexually transmitted bacterial agents. What distinguishes it from other organisms is its intracellular reproductive cycle. Up to now, four antigens have been identified in the Chlamydia genus: genus-specific antigen as well as species-specific, type-specific and subspecies-specific. C. trachomatis is a powerful immunogen which stimulates the host’s immunological processes. The intracellular parasitism of the bacteria is the basis for both symptomatic or asymptomatic infection as well as for chronic ones. The primary infection leads to a local inflammatory reaction due to penetration and reproduction of the bacteria in the epithelial cells and to IgA secretory antibody production. In most cases the host’s reaction to the primary infection is transient and does not cause tissue damage. In the course of chronic infection or reinfection, the most important processes are those of delayed hypersensitivity, which lead to a fast and intense immunological reaction of specifically sensitized Th1 lymphocytes. This reaction leads to progressive damage of the epithelial cells and to cicatrization and fibrosis, which means irreversible complications. Interferon gamma is of special importance in the process of C. trachomatis infection. High concentrations of it inhibit the bacteria’s reproductive cycle, while lower concentrations promote the development of atypical, non-contagious forms of Chlamydia of diminished metabolic activity and altered antigenicity. The chlamydial heat shock proteins are considered to be of great importance lately. Their molecular weights of 60 and 10 kDa are a powerful stimulant of immunological reactions and show significant homology (40-90%) to human and other bacterial heat shock proteins.
Keywords: Chlamydia trachomatis, primary infection, latency, reifection.
- Viruses as Hijackers of PML Nuclear Bodies
Andreas Möller and M. Lienhard Schmitz (Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland)Abstract. Promyelocytic leukemia nuclear bodies (PML-NBs) are discrete interchromosomal macromolecular structures. The integrity of this dynamic nuclear subcompartment critically depends on the presence of the name-giving PML protein. Among the permanent or transient residents of PML-NBs are various regulatory proteins, including Sp100, CBP, pRb, HIPK2, RAD51 and p53. PML-NBs are frequently targeted by viral infections, as a number of different RNA and DNA viruses including herpesviruses, adenoviruses, papovaviruses, papillomaviruses and arenaviruses cause changes in PML-NBs. Viruses interfere with PML-NB in two ways: 1) some viral proteins can associate with PML-NB proteins and/or lead to the destruction and lysis of this subnuclear compartment, thus aiding viral gene expression and disabling the host’s innate immunity; 2) the parental genomes of some nuclear-replicating DNA viruses associate preferentially with PML-NBs, which presumably serves to assist in viral gene expression or replication. Here we feature the different viral strategies leading to the hijacking of PML-NBs and discuss the consequences for the immune response.
Keywords: promyelocytic leukemia (PML), PML nuclear bodies, virus infection, SUMO, nuclear bodies.
- Quantitative Real-Time PCR in Cancer Research
Simone Mocellin, Carlo R. Rossi (Surgery Branch, Department of Oncological and Surgical Sciences, University of Padova, Italy) and Francesco M. Marincola (Immunogenetics Laboratory, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA)Abstract. In the era of the Human Genome Project, quantitation of gene expression by tumor/host cells is of paramount importance to investigate gene patterns responsible for cancer development, progression and response/resistance to treatment. Quantitative real-time PCR (qrt-PCR) technology has recently reached a level of sensitivity, accuracy and practical ease that support its use as a routine bioinstrumentation for gene level measurement. Several applications have been already implemented in the field of cancer research, and others are being validated, showing that this molecular biology tool can provide both researchers and clinicians with precious information concerning the behaviour of tumors. The knowledge of the biochemical principles underlying this biotechnology can be of great value to correctly interpret qrt-PCR data.
Keywords: quantitative PCR, cancer research.
- Using Knockout Mice to Study Experimental Meningitis
Robert Paul, Uwe Koedel and Hans-Walter Pfister (Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Germany)Abstract. Despite the use of antibiotics, the prognosis of bacterial meningitis is still poor due to central nervous system (CNS) complications, such as brain edema formation, cerebrovascular alterations, and intracranial hemorrhage. Experimental studies with animal models have given new insights into its pathophysiology during the acute phase of the disease. In recent years, genetically engineered mice have become a powerful tool in investigating the role of particular genes by targeted deletion and have also been applied in bacterial meningitis research. By using knockout mice, new knowledge of the roles of the different cytokines, proteases, and oxidants involved in the inflammatory cascade has emerged. In the future, temporal and cell type-specific control of gene expression will provide even more information on the impact of a particular gene on meningitis-induced brain damage.
Keywords: bacterial meningitis; animal model; knockout mice; inflammation; CNS.
Experimental and Clinical Immunology
- The Effect of Short-Term and Chronic Glucocorticoid Therapy on Lymphocyte Glucocorticoid Receptor Number in Patients with Asthma
Alicja Grzanka and Barbara Rogala (Chair and Clinical Department of Internal Diseases, Allergology and Clinical Immunology Medical University of Silesia, Katowice, Poland)Abstract. Glucocorticoid (GCs) hormones are widely used in the treatment of bronchial asthma. However, not all aspects of their pharmacological effects are well understood as yet. It is know that the effects of GCs are mediated through GC receptors (GCRs). We sought to evaluate the effect of short-term and chronic GC therapy on GCR number in peripheral blood lymphocytes, the relationship between GCR number and cortisol concentrations in asthma patients treated with GCs as well as the response to GC therapy in various pictures of this disease. Sixty-nine patients with bronchial asthma were investigated. Thirty-five of them had received steroid therapy: 18 patients for 1 to 15 years and 17 patients for 13 days after a prior 3 month discontinuation of steroid treatment. The control group consisted of 28 healthy, age matched volunteers. GCR numbers were determined using tritriated dexamethasone as a ligand. The scatchard method was applied to calculate the maximal specific binding and the dissociation constant. The number of receptor sites per lymphocyte was calculated. Cortisol was measured by radioimmunoassay. Lymphocyte GCR numbers in patients with bronchial asthma who were not treated with steroids, did not differ from age-matched healthy persons (means 8115±812 and 7905±832). A significant decrease in receptor number was seen in patients receiving steroid therapy (mean 4331±1041). There was also a significant difference in receptor number between the groups with short-course (mean 3741±549) and chronic steroid therapy (mean 4885±1095). The number of GCRs did not correlate with age, sex, clinical state or serum cortisol concentration in either group.
Keywords: bronchial asthma, glucocorticoid therapy, glucocorticoid receptor.
- CD30 Expression on Allergen- and Non-Allergen-Specific T Cell Lines and Its Role in Cytokine Production
Maciej Tarkowski (Department of Immunotoxicology, Institute of Occupational Medicine, Łódź, Poland)
Abstract. The main interest in CD30 has mainly focused on its ability to discriminate between T helper (Th)2 and Th1 subpopulations. The role of CD30 as the marker for Th2 cells is still controversial, which may be due to the fact that the expression and the role of CD30 is not fully understood. The data presented in this paper provides information on the expression and activity of CD30 in T cell lines specific to allergen or tuberculin-purified protein derivative (PPD) as the model of Th2 or Th1 responses, respectively. The results have shown that CD30 expression was the highest on T cells stimulated with antigen in the presence of interleukin (IL)-12 and it was present on both cell lines, regardless of antigen specificity. Activation of the CD30 receptor on CD4+ T cells, however, showed differences in mRNA expression for IL-4 between these cells. IL-4 mRNA was induced by CD30 costimulation at the same level as was obtained with anti-CD28 agonistic antibodies in allergen-specific T cells. In PPD-specific T cells this effect was not observed. Additionally, there was no effect of anti-CD30 stimulation on IL-6 mRNA expression in any of the cell lines. Comparison of protein cytokine levels for IL-4 and interferon (IFN)-gamma have shown that the highest production of IL-4 was obtained from allergen-specific T cells costimulated with anti-CD28. Although this effect was much lower in the case of CD30 costimulation, it was still above that the anti-CD3 activation alone. No effect of CD30 activation was observed in regard of IFN-gamma mRNA or protein expression in any cell line. The results of the study showed that CD30 receptor is not exclusively present on Th2 cells; however its activity may promote a Th2-dependent reaction by modulating IL-4 production.
Keywords: CD30, T cells, Th1, Th2.