CONTENTS
Review
- Human Natural Killer Cells
ISABEL BARĂO and JOĂO L. ASCENSĂOAbstract. Human natural killer (NK) cells comprise 10 to 15% of peripheral blood lymphocytes, characterized by their morphologic appearance of large granular lymphocytes (LGLs) and phenotype CD3– CD56+ CD16+ or CD16–. Functionally, these cells are defined by their ability to lyse target cells without prior sensitization and without restriction by major histocompatibility (MHC) antigens. These cells play an important role in immune defenses, especially after hematopoietic transplantation. They contribute to the defenses against virus-infected cells, graft rejection, and neoplasias; they also participate in the regulation of hematopoiesis through cytokine production and cell to cell interaction. In this mini-review we attempt to summarize the most relevant findings about these cells in terms of their origin and differentiation, their cell surface characteristics including activation and their cytolytic pathway. We have also provided a brief approach of their potential clinical use. Increased knowledge of NK cell differentiation, ontogeny and regulatory mechanisms may be of use for the planning of immunotherapeutic strategies.
Keywords: ontogeny; NK cells; cytokines; transplantation; cytotoxicity. cytotoxicity.
Immunopharmacology
- Immunoregulatory Effects of a Nutritional Preparation Containing Bovine Lactoferrin Taken Orally by Healthy Individual
MICHAL ZIMECKI, ANDRZEJ WŁASZCZYK, PASCAlE CHENEAU, ANNE-SYLVIE BRUNEL, JÖEL MAZURIER, GENEVIEVE SPIK and ANDRZEJ KÜBLERAbstract. . The aim of this study was to monitor several immune parameters in 17 healthy volunteers taking orally commercially available capsules containing bovine lactoferrin (BLFT) for 10 days (40 mg of BLFT daily). We determined leukocyte number and content of main blood cell types, spontaneous and phytohemagglutinin A (PHA)-Induced proliferation of lymphocytes, plasma levels of interleukin 6 (IL-6) and tumor necrosis factor ( (TNF-() as well as spontaneous and lipopolysaccharide (LPS)-Induced production of these cytokines in peripheral blood cell cultures. All measurements were performed before, one day and 14 days following cessation of BLFT treatment. We established some, transient drop in the percentage of neutrophils accompanied by an opposite phenomenon with regard to lymphoeyte levels. More profound changes were registered in the percentage of other cell types, for example a 100% increase in the level of immature cell forms (bands) was noted. At the same time the percentages of eosinophils and monocytes declined significantly. All these changes were, however, more individual and regulatory, the direction of these changes depended on initial picture of blood cells. Although the proliferative response of lymphoeytes showed, on avarage, a transient decrease, differentiated effects of BLFT treatment were observed depending on initial ability of lymphoeytes to proliferate. TNF-( serum levels showed a tendency to decrease during the monitoring time, the changes of IL-6 levels were, however, not significant. As in the case of the proliferative response, the treatment with BLFT was regulatory with respect to serum TNF-( levels. When we analyzed spontaneous and LPS-induced cytokine production in cell cultures we found that mainly the mean spontaneous response was affected (Inhibition). We also observed a typical, regulatory action of BLFT on the level of spontaneously produced IL-6. This kind of regulatory action of BLFT was also found in the case of spontaneously produced TNF-(. In cell cultures. The influence of other ingredients such as selenium or vitamins, contained in the capsules, cannot be excluded, although our latest data showed that orally taken bovine lactoferrin alone can induce identical changes as BLFT. Taken together, we revealed regulatory effects of oral treatment with commercially available capsules, containing BLFT. The results indicate that oral administration on BLFT-coiitaining capsules mav regulate some immune parameters in healthy individuals. In addition, the data suggest that bovine lactoferrin may be applied in clinic to improve the immune status of patients.
Keywords: : bovine lactoferrin; immunoregulation; blood cells; proliferation; interleukin 6; tumor necrosis factor .rosis factor .
- Does Moxonidine Increase Cytotoxic Activity of Ethanol in Rats? Preliminary Report on the Base of the Ultrastructural Study
KRZYSZTOF MARCZEWSKI, JANINA HALLIOP, PIOTR DZIEMIDOK, ELŻBIETA KORCZAK, DANIELA OBUCHOWSKA-PRZEBIROWSKA, ALINA TOCHMAN and AGNIESZKA SIEMIONOWAbstract. Combined effects of moxonidine and ethanol on ultrastructure of selected Wistar-Kyoto rat organs (kidney, liver, heart) were investigated. In cells of the animals, which received moxonidine alone, no morphological changes were found. In the group of rats which received alcohol, several typical submicroscopical changes were found, especially related to the mitochondria. After the combined administration of ethanol and moxonidine the pathological changes were bigger than those found in animals which received alcohol alone. Those changes were particularly significant in kidney and liver. The results might indicate that moxonidine increased cytotoxic activity of ethanol on several organs in rats.
Keywords: kidney; liver; heart; electron microscopy; moxonidine; ethanol; Wistar rats.r rats.
Cellular Immunology
- Epithelial-Mesenchymal Cell Interactions and Participation of the Neuroendocrine Markers in Tumor Development. Immunohistochemical Study
ALBINA ŻÓŁTOWSKA, JAN STĘPIŃSKI, JARZY KUCZKOWSKI, MACIEJ KAMIŃSKI, BOGUSŁAWA CYNOWSKA and WIESŁAW KRUSZEWSKIAbstract. Existence of the organ stem cell population seems to decide on ability of the tissue to regenerate and, likewise, on carcinogenesis. The source of the organ specific stem cells may be perivascular mesenchyma of thin-walled vascular channels. Our previous study on the breast cancer indicates that the perivascular mesenchyma of thin-walled vessels appears to be source of myoid cells (myofibroblasts) from which cancer cells arise. Similar results have been observed in the cancers of lung, salivary gland and colon, investigated in the current study. The perivascular cells of thin-walled channels are the source of myoid cells with expression of synaptophysin (Syn) and/or chromogranin A (Chg A), and from these cells neoplastic cells could originate. Syn and/or Chg A positive neoplastic cells were particularly well visible in connection with the vascular channels on the peripheries of tumors while other parts of tumors were only weak positive or negative for those neuroendocrine markers. Similarly as in breast cancers, the S100-protein positive dendritic cells with various of distribution were seen, expressing intimate connection with neoplastic cells. The epithelial pearls especially abundant in non-small cell lung carcinomas demonstrated immunohistochemical analogy to Hassall’s bodies: they had monocytogenic cell inside and they displayed thymosin alpha 1 (TA1), as well as mucin secretion and minute calcification. Some epithelial cells expressed desmin and Syn. All types of investigated cancers demonstrated TA1. Results of our present study suggest that the perivascular cells have a differentiation defect. Such defect may initiate abnormal stromal environment, commonly observed in neogenesis, however, the presence of thymic growth factors may favor tumor growth.
Keywords: : stromal environment; synaptophysin; chromogranin A; S100-protein; epithelial pearls.helial pearls.
- Myoid Cells and Neuroendocrine Markers in Myasthenic Thymuses
ALBINA ŻÓŁTOWSKA, TADEUSZ PAWEŁCZYK, MACIEJ STOPA, JAN SKOKOWSKI, JAN STĘPIŃSKI, ANDRZEJ ROSZKIEWICZ and WALENTY NYKAAbstract. We have studied myoid cells in normal and myasthenic thymuses as well as in thymomas. For the presence of neuroendocrine maikers-producing cells and identification of synaptophysin (Syn) the immunohistochemical method and immunoblot analysis were used. Myoid cells can be demonstrated in the thymus of myasthenic patients in high number. These cells occur in the vicinity of Hassall’s bodies but also within them. Some regenerated Hassall’s bodies displayed majority of myold cells with their concentric arrangment around the centrally situated lacunar-like cell with nuclei of monocytogenic origin. Such phenomenon may suggest cooperation of myoid cells and their epithelial transitional forms with monocytogenic cells in various thymic hormone production. It is likely that myoid cells are the source of some thymic epithelial cells. According to some authors, thymomatous epithelial cells and skeletal muscle share a common epitope defined by a monoclonal antibody (mAb), whereas thymic epithelial cells possess acetylocholine receptor (AChR) on their surface. The epithelial cells of some thymomas express also desmin. In normal thymuses of children, Syn and chromogranin A (Chg A) were demonstrated in some cells of Hassall’s bodies by immunohistochemical method. In addition, antibodies to Syn stained nerve structures surrounding the thymic blood vessels. In myasthenic thymuses, Syn expression was in cortical and medullary epithelial cells, in myoid cells and only scanty and focal in keratinized epithelial cells of Hassall’s bodies. The epithelial cells of some thymomas also express Syn. In some thymuses of all groups investigated in this study Chg A was seen in single cells of Hassall’s bodies and focally in cortical epithelial cells. Our results show that in normal thymuses of cardiac surgery patients and in the adult myasthenic thymuses antibody raised against Syn recognized protein with molecular weight of 48 000 but not normal (38 000) Syn. It remains to be elucidated if the overexpression of synaptophysin-like protein in myasthenic thymuses is a compensatory phenomenon to the defect in normal synaptic function.
Keywords: myasthenia gravis; thymus; myoid cells; synaptophysin; immunohistochemical and immunoblot analysis.blot analysis.
Experimental Oncology
- Insertion of the IL-2 Gene Decreases Tumorigenicity of Murine Fibrosarcoma
HALINA KU?NIERCZYK, PIOTR ZAŁĘCKI, ELŻBIETA PAJTASZ-PIASECKA and CZESŁAW RADZIKOWSKI
Abstract. Murine interleukin 2 (mIL-2) cDNA was introduced through lipofection into cells of murine F-69-3 fibrosarcoma line established in vitro from tumors induced chemically in athymic mice. Using a modified MTT bloassay in CTLL-2 indicator line the F-69-3/IL-2 transfectants were found to secrete between 650 – 1750 laboratory units (LU) of IL-2/5 x 105 cells/48 h in restricted culture conditions. When inoculated subcutaneously to immunocompetent BALB/c or CD2F1 mice, the transfected cells showed reduced tumorigenic potential as compared with parental F-69-3/wt or control F-69-3/neo cells. The rejection of F-69-3/IL-2 tumors required an intact immune system as they grew progressively in athymic mice. The majority of immunocompetent mice that rejected IL-2 secretors were found to be protected against subsequent challenge with parental cells. These preliminary results suggest that IL-2-transfected murine fibrosarcoma could be used as a model for studying mechanisms underlying the antitumor immune response.
Keywords: F-69-3 fibrosarcoma; parental tumor cells; interleukin 2-secreting tumor cells; rejection.ls; rejection.