A komplementrendszer immunfunkciókat szabályozó szerepe fiziológiás és kóros folyamatok során = Immunoregulatory role of complement under physiological and pathological conditions

A komplementrendszer immunvédekezésünk szerves része. A legnagyobb mennyiségben előforduló komponens, a C3 szerepe igen változatos; a patogének eliminálásától az immunválasz szabályozásáig terjed. A számos biológiai funkciót főként a C3 aktivációs fragmentumai közvetítik, amelyek különböző sejtek különböző komplementreceptoraihoz kötődnek. Célunk az volt, hogy a C3 újabb, immunfolyamatokat szabályozó szerepét feltárjuk. Kísérleteink eredményei eddig nem ismert molekuláris és sejtes mechanizmusokra derítettek fényt, egyrészt a limfociták CR1 által közvetített gátlásának további tanulmányozásával, másrészt az antigénbemutató sejtek funkcióival kapcsolatban. Vizsgálataink során autoimmun betegek (RA és SLE) sejtjeit is vizsgáltuk, valamint az SM egér-modelljét, az EAE-t is tanulmányoztuk. Eredményeink nemcsak azért fontosak, mert általuk jobban megértjük az alapvető immunfolyamatokat, hanem azért is, mert egyes autoimmun-betegségek kezelésében reménykeltő cél-molekulát sikerült azonosítanunk. Eredményeinket számos ""peer-reviewed"" cikkben közöltük (össz-IF: 66), továbbá a projekt anyagából két PhD-fokozat született és további kettő folyamatban van. Eredményeink arra sarkalltak, hogy kutatásainkat kiterjesszük a munkatervben nem részletezett területre is, melynek során Dr. Prechl Józseffel és Dr. Papp Krisztiánnal (MTA-ELTE Immunológiai Kutatócsoport) együttműködve mikro-array rendszert dolgoztunk ki az ellenanyag (köztük autoantitestek) általi komplementaktiválás kimutatására. | The complement system is an integral part of our immune system. The role of its most abundant protein, component C3, is very versatile – it ranges from the elimination of pathogens to the regulation of immune responses. The various biological functions are mainly mediated by the activation fragments of C3, via their interaction with different complement receptors expressed by different cell types. Our goal was to reveal new regulatory functions of C3. We have described so far unknown molecular and cellular interactions, further analysed the CR1-mediated inhibiton of lymphocyte functions and the role of C3 in the function of antigenpresenting cells. We extended our studies to autoimmune patients – such as RA and SLE -, furthermore to EAE, the mouse modell of SM. Our results are important not only beacuse they help better understand basic immunological processes, but also because we could identify a promising target-molecule for the treatment of autoimmune disorders. We published our results in peer-reviewed international journals (total IF: 66), furthermore two PhD-degrees were accomplished and further two will be obtained based on this OTKA-project. Our results urged us to extend the research to a new area, namely the development of a protein-microarray system, which can be used to detect complement activation initiated by antibodies. This work was accomplished by a cooperation with Drs. J.Prechl and K.Papp at the Immunology Research Group of the HAS at ELU

In Posidonia oceanica cadmium induces changes in DNA methylation and chromatin patterning

In mammals, cadmium is widely considered as a non-genotoxic carcinogen acting through a methylation-dependent epigenetic mechanism. Here, the effects of Cd treatment on the DNA methylation patten are examined together with its effect on chromatin reconfiguration in Posidonia oceanica. DNA methylation level and pattern were analysed in actively growing organs, under short- (6 h) and long- (2 d or 4 d) term and low (10 μM) and high (50 μM) doses of Cd, through a Methylation-Sensitive Amplification Polymorphism technique and an immunocytological approach, respectively. The expression of one member of the CHROMOMETHYLASE (CMT) family, a DNA methyltransferase, was also assessed by qRT-PCR. Nuclear chromatin ultrastructure was investigated by transmission electron microscopy. Cd treatment induced a DNA hypermethylation, as well as an up-regulation of CMT, indicating that de novo methylation did indeed occur. Moreover, a high dose of Cd led to a progressive heterochromatinization of interphase nuclei and apoptotic figures were also observed after long-term treatment. The data demonstrate that Cd perturbs the DNA methylation status through the involvement of a specific methyltransferase. Such changes are linked to nuclear chromatin reconfiguration likely to establish a new balance of expressed/repressed chromatin. Overall, the data show an epigenetic basis to the mechanism underlying Cd toxicity in plants

Comparing the effects of excess copper in the leaves of Brassica juncea (L. Czern) and Brassica napus (L.) seedlings: Growth inhibition, oxidative stress and photosynthetic damage

Hydroponic experiments were conducted to compare the effects of excess copper (Cu) on growth and photosynthesis in young Indian mustard (Brassica juncea) and oilseed rape (Brassica napus). We compared the effects of excess Cu on the two Brassica species at different physiological levels from antioxidant levels to photosynthetic activity. Nine-day-old plants were treated with Cu (10, 25 and 50 μM CuSO4) for 7 and 14 days. Both species took up Cu from the external solution to a similar degree but showed slight root-to-shoot translocation. Furthermore, after seven days of treatment, excess Cu significantly decreased other microelement content, such as iron (Fe) and manganese (Mn), especially in the shoots of B. napus. As a consequence, the leaves of young Brassica napus plants showed decreased concentrations of photosynthetic pigments and more intense growth inhibition; however, accumulation of highly reactive oxygen species (hROS) were not detected. After 14 days of Cu exposure the reduction of Fe and Mn contents and shoot growth proved to be comparable in the two species. Moreover, a significant Cu-induced hROS accumulation was observed in both Brassica species. The diminution in pigment contents and photosynthetic efficiency were more pronounced in B. napus during prolonged Cu exposure. Based on all the parameters, B. juncea appears to be more resistant to excess Cu than B. napus, rendering it a species with higher potential for phytoremediation

Expression pattern of the human ABC transporters in pluripotent embryonic stem cells and in their derivatives

Background: ATP-binding Cassette (ABC) transporters have key roles in various physiological functions as well as providing chemical defense and stress tolerance in human tissues. In this study we have examined the expression pattern of all ABC proteins in pluripotent human embryonic stem cells (hESCs) and in their differentiated progenies. We paid special attention to the cellular expression and localization of multidrug transporter ABC proteins. Methods: Stem cell differentiation was carried out without chemical induction or cell sorting, and specialized cell types were separated mechanically. Cellular features regarding pluripotency and tissue identity, as well as ABC transporter expression were studied by flow cytomtery, immuno-microscopy and qPCR-based low-density arrays. Results: Pluripotent hESCs and differentiated cell types (cardiomyocytes, neuronal cells and mesenchymal stem cells) were distinguished by morphology, immunostaining markers and selected mRNA expression patterns. We found that the mRNA expression levels of the 48 human ABC proteins also clearly distinguished the pluripotent and the respective differentiated cell types. When multidrug and lipid transporter ABC protein expression was examined by using well characterized specific antibodies by flow cytometry and confocal microscopy, the protein expression data corresponded well to the mRNA expression results. Moreover, the cellular localization of these important human ABC transporter proteins could be established in the pluripotent and differentiated hESC derived samples. Conclusions: These studies provide valuable information regarding ABC protein expression in human stem cells and their differentiated offspring. The results may also help to obtain further information concerning the specialized cellular functions of selected ABC transporter

FSCPX, a chemical widely used as an irreversible A1 adenosine receptor antagonist, modifies the effect of NBTI, a nucleoside transport inhibitor, by reducing the interstitial adenosine level in the guinea pig atrium

L

Szívtranszplantáció vagy abláció?: tachycardia-indukálta cardiomyopathia

L

Szívtranszplantáció vagy abláció?: tachycardia-indukálta cardiomyopathia

L