CONTENTS
Mini-Review
- Mechanism of Joint Destruction in Rheumatoid Arthritis
GAYE CUNNANE, KLAUS M. HUMMEL, ULF MULLER-LADNER, RENATE E. GAY and STEFFFN GAYAbstract. The synovium in rheumatoid arthritis (RA) is characterized by an increase in lining layer thickness and infiltration of inflammatory cells into the sublining area. Fibroblasts in the lining layer develop the appearance of “transformed cells”, under the influence of proto-oncogenes involved in the regulation of the cell cycle. Fibroblast and macrophage-derived cytokines such as IL-1 and TNF-a are present abundantly in the rheumatoid synovium and stimulate these cells to produce destructive enzymes. Other cytokines such as IL-4 and IL-10 represent a physiological attempt to reverse the inflammatory process. Adhesion molecules facilitate both the migration of cells to the joint as well as the attachment of synovium to bone and cartilage. Joint destruction is mediated by enzymes such as serine proteases, matrix metalloproteinases (MMPs) and the cathepsins. Treatments directed against various components of the inflammatory cascade have shown promise. Inhibition of MMPs or adhesion molecules, blockade of IL-1 or TNF-a and the use of anti-Fas antibodies to induce apoptosis offer new possibilities for the treatment of RA. More recently, the employment of genes with antlarthritic properties has shown therapeutic potential.
Keywords: rheumatoid arthritis; synovium; oncogenes; cytokines; adhesion molecules.
Cellular Immunology
- Surface Phenotypes of Human T Cell Lines Generated after WGA- and PHA-Stimulation
JAN KONRAD SIWICKI, HENRYK SKURZAK and JAN A. STEFFENAbstract. We have reported earlier that human T lymphoeytes from blood or spleens of normal donors can be propagated in long-term culture in the presence of IL-2, after stimulation either with wheat germ agglutinin (WGA) or phytohemagglutinin (PHA) and with the use of repeated restimulation with supernatants collected after 24 h of such cultures. In the present study we demonstrate that lymphoblast lines generated with this method contain predominantly the cells expressing CD3 molecule and a b heterodimer of T cell receptor (TcRa b ). In PHA-initiated lymphoblast lines CD4– CD8+ cells prevailed, whereas in lymphoblast lines generated after WGA-stimulation various proportion of CD4– CD8+, CD+ CD8– and CD4– CD8– cells were found. In some cell lines a gradual selective outgrowth of TcRa b CD4+ CD8– or CD4– CD8– cells was observed. These data indicate that the long-term growth potential of human normal T lymphoblasts is not restricted to a single subset and that the surface phenotypes acquired during differentiation of the cells can be retained even after more than 100 population doublings in culture.
Keywords: T cell; long-term growth; phenotype.
- Effect of Heparin on the Course of Sulphur Dioxide Induced Bronchitis in Rats
MARYLA KRASNOWSKA, ARTUR KWAŚNIEWSKI, JERZY RABCZYŃSKI, ANDRZEJ FAL and JAN KURYSZKOAbstract. The aim of this study was to investigate the effect of heparin on the rat bronchial mucosa changes induced by sulphur dioxide (S02) inhalation. Sixty five rats were used in this experiment. Five of them constituted a control group, while 60 were exposed to SO2. Forty of the latter subgroup were additionally treated with low molecular weight heparin (LMWH), either during or after terminating exposure to SO2. In all animals exposed to S02 inflammatory cells were found in broncho-alveolar lavage fluid (BALf) in numbers significantly higher from those observed in healthy controls. The rats exposed to S02 and treated with LMWH showed intermediate cell pattern in the bronchi between healthy and S02– exposed animals. When comparing histological picture of the bronchi, we noted extensive changes in irritated rats. These changes were either less expressed or totally absent in animals treated with heparin. The activity of enzymes: acid phosphatase (ACP), alkaline posphatase (AP) and lactate dehydrogenase (LDH) rose in BALF, although the rise was not parallel and did not correlate with the magnitude of cellular influx or histological changes. Heparin did not influence this changes.
Keywords: heparin; sulphur dioxide; bronchitis in rats; bronchoalveolar lavage fluid enzymes.nzymes.
Clinical Immunology
- Changes in Soluble IL-6 Receptor and IL-6 Production by Polymorphonuclear Cells and Whole Blood Cells of Breast Cancer Patients
EWA JABŁOŃSKA and ZOFIA PIETRUSKAAbstract. The release of soluble interleukin 6 receptor (IL-6sR) and interleukin 6 (IL-6) was investigated in polymorphonuelear and whole blood cell cultures from untreated patients with breast cancer. IL-6sR and IL-6 were determined in the culture supernatants by a sensitive enzymoimmunological assay. We have shown a decreased ability of unstimulated and stimulated polymorphonuclear cells (PMNs) and whole blood cells (WBC) of cancer patients to release IL-6sR in comparison to a control group. Simultaneously, we have also found an increased capacity of unstimulated cells from the patients to produce of IL-6. The used stimulators zymosan and lipopolysaccharide (LPS) resulted in increased IL-6sR secretion by PMNs and WBC of patients but did not influence IL-6 production by the same cells. We have also determined the levels of IL-6sR and IL-6 in the sera of cancer patients. The mean concentrations of IL-6sR and IL-6 in the sera of patients were higher than those in the control group. We have not noticed any correlations in the culture supernatant and serum levels of IL-6sR or IL-6 between control and cancer patient groups.
Keywords: breast cancer; polymorphonuclear cells; whole blood cells; interleukin 6 (IL-6); soluble IL-6 receptor.IL-6 receptor.
- Association between Longevity and Allelic Forms of Human Leukocyte Antigens (HLA): Population Study of Aged Italian Human Subjects
GIORGIO RICCI, CLARA COLOMBO, BARBARA GHIAZZA and MARIA TERESA ILLENIAbstract. Several arguments support the idea of a link between longevity and heredity, both in humans and in experimental animals. We have therefore investigated the possibility of an association between the human leukocyte antigens (HLA) and longevity in two groups of Italian subjects: 108 healthy subjects over 85 years old, and 749 healthy blood donors (controls). Only four antigens showed a higher frequency in the elder group: HLA-A31(19), B7, Cw7 and DQ1 These findings suggest an involvement of HLA antigens in human longevity, but the real biological meaning of these results is still unclear.
Keywords: longevity; human leucocyte antigens (HLA). (HLA).
- Lymphocyte Interactions with Extracellular Matrix Proteins and Endothelium in Renal Allograft Recipients
MARIA NOWACZYK, ANDRZEI GÓRSKI, GRAŻYNA KORCZAK-KOWALSKA, PIOTR WIERZBICKI, JANUSZ WYZGAL, MAGDALENA DURLIK and ANNA ORŁOWSKAAbstract. Recent data indicate that extracellular matrix (ECM) proteins can provide costimulatory signals during the process of T cell activation. Those proteins accumulate in situ during allograft rejection; therefore, it may be expected that local ECM: T cell interactions may be relevant in the immunopathology of rejection. T cell adhesion from allograft of recipients with stable renal function (RAR-S) and patients with biopsy-proven chronic rejection (RAR-CH) to ECM proteins (collagen type IV, fibronectin, elastin) was measured. Furthermore, T cell: endothelial interactions in vitro were studied. Adhesion of PHA-activated T cells from both groups of allograft recipients to fibronectin, collagen type IV and elastin was significantly lower than in healthy blood donors. Moreover, similar pattern of activity was observed when T cell attachment to resting and activated endothelium was studied. There were no significant differences in the number of circulating CD45RO and CD4 positive T cells. We observed a higher (although not significantly) adhesion of the T cells to resting human dermal microvascular endothelial cells (HMEC) in the chronic stages of rejection, which can suggest that the immunosuppressive protocol used in the treatment of chronic rejection is insufficient to control immunopathologic phenomena occurring in that process. Therefore, it may be argued that too low immunosuppression can be one of the factors responsible for the development of this complication.
Keywords: interactions; lymphocyte; extracellular matrix; endothellum; allograft.um; allograft.
- Application of Microsatellite Markers for Monitoring of Reconstitution Pattern in Patients after Bone Marrow Transplantation/Peripheral Blood Progenitor Cell Transplantation
MALGORZATA JUNGERMAN, MARIOLA SĘDZIMIRSKA, ANDRZEI LANGE, and MICHAŁ WITT’Abstract. We present data on application of microsatellite markers for detection of complete vs. mixed chimerism in individuals after bone marrow transplantation (BMT) and peripheral blood progenitor cell transplantation (PBPCT). Genotypes of the peripheral blood or bone marrow cells of three donor/recipient pairs were studied at several microsatellite loci. In two cases we identified complete chimerism in recipients’ peripheral blood and bone marrow after transplantation. These two patients were alive with no symptoms of disease relapse and/or transplant rejection long time after BMT or PBPCT. In the third patient we observed mixed chimerism with the prevalence of donor’s genotype while she was alive and well and the prevalence of recipient’s genotype when she relapsed and required interferonotherapy. Results of our molecular studies correlated with the patients’ clinical outcome. We show that molecular detection of mixed chimerism may be used for prediction of relapse in patients after BMT or PBPCT.
Keywords: bone marrow transplantation; mixed chimerism; microsatellite markers.llite markers.
Various
- Reappraisal of Amiloride Action on Transepithelial Electrical Potential Difference of Isolated Tracheal Wall
TOMASZ TYRAKOWSKI, BOLESŁAW BANACH, ARTUR MO?CIBRODA, MIROSŁAWA BARTŁOMOWICZ and MAŁGORZATA WOJCIECHOWSKAAbstract. The action of amiloride on two different components of airway electrical potential difference, one stable (PD) and the other transiently hyperpolarizable after gentle mechanical stimulation (dPD), was studied by means of isolated tracheal wall mounted in a modified Ussing apparatus. The immediate effect of amiloride, when added to the bathing and stimulating medium, was a partial depolarization, and a diminution or elimination of dPD. After at least 60 min incubation of the tracheal wall with amiloride in the presence of the drug in the bathing and stimulating fluid, both the PD, and dPD were no different from the control. This difference between the immediate and the sustained action of amiloride on airway PD suggests that there is an efficient regulatory system in the airway walls which stabilizes the transepithelial PD. The usefulness of amiloride as a drug for cystic fibrosis patients is discussed in the light of these findings.
Keywords: airway; amiloride; cystic fibrosis; isolated trachea; mechanically sensitive receptor; transepithelial potential difference.al difference.
- Culture of Human Nasal Epithelial Cells from Nasal Polyps on Collagen Matrix
MAREK L. KOWALSKI, RAFAŁ PAWLICZAK, JANINA WOŹNIAK, KATARZYNA SIUDA, JANINA GRZEGORCZYK, MARTA PIETRZAK, ZBIGNIEW KOZŁOWSKI and KRYSTYNA MAREKAbstract. Epithelial cell cultures became an experimental model employed for both animal and human studies. We established a modified method of culture of human nasal epithelial cells from nasal polyps using serum-free, hormonally supplemented Ham’s F-12 medium and Vitrogen 100 collagen matrix. Cells reached confluent monolayer structures in 5 to 7 days (mean time 6 + 0.89 days) of culture. The confluent cultures consisted of pure epithelial cells, which was confirmed by light and electron microscopy, and immunohistochemical staining with anticytokeratin antibody. The success ratio of cultures was 61.5%. The culture system described is efficient enough to provide pure epithelial cells for further functional studies.
Keywords: nasal polyps; human nasal epithelial cells; culture, in vitro; collagen matrix.llagen matrix.
- Average Quantitative Concentration of Cotinine within the System Pregnant Woman-Baby
DOROTA DOBEK, ANDRZEJ KARMOWSKI, KRZYSZTOF A. SOBIECH, ŁUKASZ TERPIŁOWSKI and MAGDALENA MI?-MICHAŁEK
Abstract. The findings presented by the authors of this report contribute to the diagnosis of pathology of pregnancy i.e. they assess the influence of nicotine on the organisms of a mother and a new-born child, estimated by concentration of cotinine, the most important metabolise of nicotine. The mean proportional share of citinine in the fluids and organs in the pregnant women smoking actively was as follows: urine 72.1 %, amniotic fluids 14.3%, colostrum 8.9% and placenta 4.7%. The authors pay a particular attention to the “colostrum-milk way” in the mother-child relationship what is emphasized in this report.
Keywords: cotinine; pregnancy; biological fluids.ogical fluids.