CONTENTS
Review
- Involvement of Fas/FasL System in the Pathogenesis of Autoimmune Diseases and Wilson’s Disease
GIORGIO STASSI, VALENTINA DI FELICE, MATILDE TODARO, FRANCESCO CAPPELLO, GIOVANNI ZUMMO, FELICIA FARINA, MASSIMO TRUCCO and RUGGERO DE MARIAAbstract. The interaction of Fas with FasL has been demonstrated to be implicated in the pathogenesis of several autoimmune and liver diseases. Recently, attention has been focused on the hypothesis that thyrocytes and b cells undergo massive Fas/FasL?mediated apoptosis during autoimmune response. Similarly, hepatocyte cell death occurring following copper accumulation points towards the same mechanism.
Keywords: autoimmune diseases; apoptosis; Fas; Hashimoto’s thyroiditis; Wilson’s disease; insulin?dependent diabetes mellitus.
- Virokines: Mediators of Virus?Host Interaction and Future Immunomodulators in Medicine
GIRISH J. KOTWALAbstract. A decade ago, after the discovery of the major secretory protein of vaccinia virus with structural similarity to complement control, the term virokine was coined. The term virokine, simply refers to a virally encoded secretory protein. During the past decade several virokines were discovered and most of them have been found to have immunomodulatory effects. A subset of virokines which resemble cytokine/chemokine receptors have been termed viroceptors. Examples of viroceptors include the TNF receptor homolog and the IL?1b receptor homolog. During the past several years animal models have been developed to try to understand the in vivo role of the virokines. It has become evident from at least two studies that quite a few of the virokines down?regulate the inflammatory response elicited during infection. This down?regulation at least in one model system seems to indicate that it ensures the preservation of the viral habitat (site of infection). One obvious spinoff of the research on virokines is a new class of immunomodulators has become available as therapeutics in alleviating the symptoms of inflammatory disease conditions.
Keywords: virokines; viroceptors; virus?host interaction; virokine therapeutics.
- How Does the Major Histocompatibility Complex Influence Behavior?
EDELGARD JANSSEN and NICHOLAS ZAVAZAVAAbstract. The major histocompatibility complex (MHC) encodes highly polymorphic cell surface glycoproteins that form the basis of immunological individuality. It has been postulated that MHC besides its role in immune defence also determines behavior through formation of specific odor cues. In addition several studies have implicated MHC disassortative odor and mating preferences in mice, rats, and humans. Further leading studies have suggested that mice and humans prefer to mate with MHC dissimilar individuals. Although the latter remains controversial, MHC dependent mating preferences provide a potentially important selective factor driving the polymorphisms of the MHC genes. Here we review some of the available data and hypotheses on the influence of the MHC on behavior and discuss its molecular and chemical basis.
Keywords: major histocompatibility complex; human leukocyte antigen; odor; individual chemosignals; perception; mate choice.
- Cyclolinopeptides and Their Analogs – a New Family of Peptide Immunosuppressants Affecting the Calcineurin System
IGNACY Z. SIEMION, MAREK CEBRAT and ZBIGNIEW WIECZOREKAbstract. The results of the investigation of immunosuppressive activity of cyclolinopeptide A (CLA – cyclic hydrophobic nonapeptide present in the linseeds) and its analogs are discussed. The results obtained for other natural cyclic peptides showing structural similarities with CLA (antamanide, cycloamanides, hymenistatin, hymenamides) are also reviewed. It results from these investigations that the molecular mechanism of the CLA action is the same as that of cyclosporin A and FK?506 compound, i. e. it consists in formation of the complex with cyclophilin and inhibition – in this form – of the phosphatase activity of calcineurin. The results also suggest that the immunosuppressive activity of these compounds resides in their –Pro?Xxx?Phe? fragment, where Xxx is a hydrophobic (e. g. Leu, Val) or aromatic amino acid residue.
Keywords: antamanide; cycloamanides; cyclolinopeptide A; hymenamides, hymenistatin; peptide immunosuppressants
Experimental and Clinical Immunology
- Nitric Oxide, Heparin and Procaine Treatment in Experimental Ceruleine?Induced Acute Pancreatitis in Rats
MAREK DOBOSZ, ZDZISŁAW WAJDA, STANISŁAW HAĆ, JOLANTA MYŚLIWSKA, EWA BRYL, LUCJANNA MIONSKOWSKA, ANDRZEJ ROSZKIEWICZ and ANDRZEJ MYŚLIWSKIAbstract. The aim of the study was to investigate the impact of L?arginine (nitric oxide donor), L?NNA (NO synthase inhibitor), heparin and procaine on the pancreas’ microcirculation, serum interleukin 6 (IL?6) level, and microscopic alterations of the pancreatic gland in acute pancreatitis (AP) in rats. AP was induced by 4 i. p. injections of cerulein (15 mg/kg/h). Microcirculatory values of the pancreas were measured by means of laser Doppler flowmetry 5 h after the first cerulein injection. Remarkable morphologic changes in the pancreas, including parenchymal necrosis, an elevation of serum IL?6 activity, and significant drop of pancreatic capillary perfusion was observed in rats with NO synthase inhibition. L?arginine improved the pancreatic microcirculation but worsened the microscopic alterations within the pancreas. Heparin had a beneficial effect on the microcirculatory values, serum IL?6 activity, and morphologic changes. Procaine had no effect on the course of AP. Authors conclude that heparin, improving the pancreatic capillary blood perfusion, may be considered as a promising therapeutic agent in acute pancreatitis.
Keywords: acute pancreatitis; microcirculation; interleukin 6; nitric oxide; heparin; procaine.
- Tumor Infiltrating Lymphocytes in HLA+ and HLA– Laryngeal Cancer – Quantitative Approach
GRZEGORZ DWORACKI, ALEKSANDRA KRUK?ZAGAJEWSKA, ELŻBIETA JEŻEWSKA, JAN SIKORA1 and JAN ŻEROMSKI1Abstract. In search of factors governing the accumulation of tumor infiltrating lymphocytes (TIL), frozen sections from fresh surgical specimens of laryngeal carcinoma (n=36) were tested by alkaline phosphatase–anti?alkaline phosphatase (APAAP) immunohistochemistry for monomorphic determinants of HLA class I and class II expression on tumor cells and for the distribution of lymphoid cells bearing CD differentiation antigens. Cell subsets were quantitated in two tumor compartments, tumor mass and tumor stroma, by computer?assisted image analysis. In a portion of examined samples lymphoid cell suspension was isolated from cancerous tissues and assessed by flow cytometry. It has been found that T cells, localized mostly in tumor stroma, were predominant cell population in the tumor microenvironment. Their ability to penetrate tumor mass but not tumor stroma, by CD8+ T cells in particular, but also by natural killer (NK) cells, was associated with HLA class I antigen expression on tumor cells. In flow cytometric analysis activated T lymphocytes (CD3+DR+) were abundant in HLA+ tumors as compared to HLA– ones. In 4 year follow up of 20 patients the mortality was higher in HLA– group but the data were not statistically significant. These results show that HLA class I expression on tumor cells favor penetration of cytotoxic lymphoid cells into tumor mass, at least in the laryngeal cancer.
Keywords: laryngeal carcinoma; HLA antigens; tumor infiltrating lymphocytes; APAAP reaction, image analysis; flow cytometry.
- Adhesion Molecule Expression Stimulated by Bacteroides thetaiotaomicron Cell?Surface Antigens
ALICJA ROKOSZ, FELICJA MEISEL-MIKOŁAJCZYK, CEZARY MALCHAR, MARIA NOWACZYK2 and ANDRZEJ GÓRSKI2Abstract. Bacteroides thetaiotaomicron, a Gram?negative anaerobic rod belonging to the Bacteroides fragilis group (BFG), is involved in many systemic and local, most frequently suppurative infections in man. The cell envelope of these rods is composed of two carbohydrate?containing antigens: lipopolysaccharide (LPS) and capsular polysaccharide (CPS). Adhesion molecules ICAM?1, VCAM?1 and E?selectin (ELAM?1) are induced on the endothelial cells by mediators of inflammation. The aim of this study was to assay the ability of B. thetaiotaomicron surface antigens to induce adhesion molecule expression on the endothelial cells. The influence of LPS and CPS on the expression of adhesion molecules on HMEC?1 cell line was examined in an ELISA test. ELISA was performed with monoclonal mouse anti?human: ICAM?1, VCAM?1 and E?selectin antibodies of the IgG class. B. thetaiotaomicron lipopolysaccharides revealed the ability to induce ICAM?1, VCAM?1 and E?selectin expression on the endothelial cells. Their activities were similar, but lower than the activity of Eschericha coli LPS. ICAM?1 was the most stimulated adhesion molecule. The strongest activation by LPS was achieved at the concentrations of 10. 0 and 1. 0 mg/ml. The ability of capsular polysaccharide to induce the expression of adhesion molecules was considerably weaker.
Keywords: adhesion molecules; endothelium; Bacteroides thetaiotaomicron; lipopolysaccharide; capsular polysaccharide
Various
- Isolation of Human Lutropin from Woman Urine and Comparison of Its Properties with Pituitary Hormone
EWA KUROWSKA and APOLINARY SZEWCZUKAbstract. Lutropin was isolated from woman preovulatory urine by immunoaffinity chromatography using a column with monoclonal antibody (mAb) anti?bhLH(37) coupled to Sepharose CL 4B. As it was demonstrated the isolated hormone, as well as pituitary lutropin, were separated in SDS?PAGE into several well visible fractions with 30–94 kDa molecular mass and scarcely visible fractions with 14–20 kDa. All fractions reacted only with mAb anti?ahCG(99) ?HRP but not with mAb anti?bhLH?HRP. Pretreatment of pituitary lutropin with PN?Gase F did not affect its electrophoretic pattern. After boiling the hormone with SDS and bME no fractions in SDS?PAGE were observed. No substantial differences in affinity chromatography on Con A?Sepharose between pituitary and urinary lutropin were noted. Some differences between these two hormone preparations were observed in assays performed with several ELISA variants. Using two pairs of mAbs anti?bhLH for ELISA technique no hormone was assayed in urine samples from women, collected between 12 and 16 days of menstrual cycles.
Keywords: human lutropin; human luteinizing hormone; urine lutropin; pituitary lutropin; affinity chromatography; SDS?PAGE; comparative assays.
- Antifungal Activity of 2-(4-Chlorophenyl)-1,2-Benzisoselenazol-3(2H)-One, the Analog of Ebselen
MAŁGORZATA BIEŃ, BARBARA BŁASZCZYK, KATARZYNA KALINOWSKA, JACEK MŁOCHOWSKI and ANNA D. INGLOTAbstract. The antimicrobial activity of 8 selenoorganic compounds (3-benzisoselenazoles, 1-benzisoselenazolone oxide and 4-disaryl diselenides) was investigated. It was found that selenoorganic compounds from benzisoselenazolone group suppress growth of some fungi and bacteria. The growth of Saccharomyces cerevisiae S127-8b and Candida albicans 258 strains was strongly inhibited by the 2-(4-chlorophenyl)-1, 2-benzisoselenazol-3(2H)-one. Also Ebselen and 2-acetyl-1, 2-benzisoselenazol-3(2H)-one caused strong inhibition of Saccharomyces cerevisiae S127-8b growth but a lower effect was observed in assays with Candida sp. strains. Benzisoselenazolones were also found to have antibacterial activities. They significantly reduced the growth of Gram-negative Escherichia coli K-12 ROW and Gram-positive Staphylococcus aureus 209P (Oxford) bacteria strains.
Keywords: selenoorganic compounds; Saccharomyces cerevisiae; Candida albicans; Staphylococcus aureus; Escherichia coli.
- Investigation of Influence of Proteus mirabilis LPS Polysaccharide Part on the Murine Immune Cells Activation
MAGDALENA KLINK, CHUNG HEE SONN, WIESŁAW KACA and YOUNG SANG KIM
Abstract. The biological activities were investigated of Proteus mirabilis lipopolysaccharides (LPSs) and their fragments, namely, the induction of nitric oxide (NO) and interleukin 1 (IL?1) synthesis by murine macrophages and the proliferation of murine spleen cells. The O?specific polysaccharide (F1), core oligosaccharide (F2) and lipid A were as effective as intact LPS in stimulating murine macrophages to produce NO. IL?1 synthesis was also induced by all studied types of endotoxins (S, Ra, Re) and partial structures, however F1, F2 and lipid A fractions required the presence of serum. In contrast to LPS, the O?specific polysaccharide, core oligosaccharide and lipid A were not able to induce the blast response of murine non?adherent splenocytes.
Keywords: Proteus mirabilis; lipopolysaccharide; nitric oxide; interleukin 1.