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排序方式: 共有86条查询结果,搜索用时 15 毫秒
1.
Krzysztof Bryniarski Wlodzimierz Ptak Emilia Martin Katarzyna Nazimek Marian Szczepanik Marek Sanak Philip W. Askenase 《PloS one》2015,10(4)
Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases. 相似文献
2.
Wojciech Szczepanik Artur Krężel Magdalena Brzezowska Ewa Dworniczek Małgorzata Jeżowska-Bojczuk 《Inorganica chimica acta》2008,361(9-10):2659-2666
The formation of copper(II) complexes of an aminoglycoside antibiotic – sisomicin – was studied by potentiometry and spectroscopic techniques (UV–Vis, CD, NMR and EPR). At physiological pH, Cu(II) is bound to both amino functions and hydroxyl oxygen of the 2-deoxystreptamine moiety. When pH increases slightly, another amino group located at the aminosugar ring becomes engaged in the coordination process. Microbiological studies with the use of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa showed that copper(II) does not interfere with the bactericidal action of sisomicin. 相似文献
3.
4.
Different defense strategies of Dendrolimus pini, Galleria mellonella, and Calliphora vicina against fungal infection 总被引:3,自引:0,他引:3
Boguś MI Kedra E Bania J Szczepanik M Czygier M Jabłoński P Pasztaleniec A Samborski J Mazgajska J Polanowski A 《Journal of insect physiology》2007,53(9):909-922
The resistance of Galleria mellonella, Dendrolimus pini, and Calliphora vicina larvae against infection by the enthomopathogen Conidiobolus coronatus was shown to vary among the studied species. Exposure of both G. mellonella and D. pini larvae to the fungus resulted in rapid insect death, while all the C. vicina larvae remained unharmed. Microscopic studies revealed diverse responses of the three species to the fungal pathogen: (1) the body cavities of D. pini larvae were completely overgrown by fungal hyphae, with no signs of hemocyte response, (2) infected G. mellonella larvae formed melanotic capsules surrounding the fungal pathogen, and (3) the conidia of C. coronatus did not germinate on the cuticle of C. vicina larvae. The in vitro study on the degradation of the insect cuticle by proteases secreted by C. coronatus revealed that the G. mellonella cuticle degraded at the highest rate. The antiproteolytic capacities of insect hemolymph against fungal proteases correlated well with the insects' susceptibility to fungal infection. The antiproteolytic capacities of insect hemolymph against fungal proteases correlated well with the insects' susceptibility to fungal infection. Of all the tested species, only plasmatocytes exhibited phagocytic potential. Exposure to the fungal pathogen resulted in elevated phagocytic activity, found to be the highest in the infected G. mellonella. The incubation of insect hemolymph with fungal conidia and hyphae revealed diverse reactions of hemocytes of the studied insect species. The encapsulation potential of D. pini hemocytes was low. Hemocytes of G. mellonella showed a high ability to attach and encapsulate fungal structures. Incubation of C. vicina hemolymph with C. coronatus did not result in any hemocytic response. Phenoloxidase (PO) activity was found to be highest in D. pini hemolymph, moderate in G. mellonella, and lowest in the hemolymph of C. vicina. Fungal infection resulted in a significant decrease of PO activity in G. mellonela larvae, while that in the larvae of D. pini remained unchanged. PO activity in C. vicina exposed to fungus slightly increased. The lysozyme-like activity increased in the plasma of all three insect species after contact with the fungal pathogen. Anti E. coli activity was detected neither in control nor in infected D. pini larvae. No detectable anti E. coli activity was found in the control larvae of G. mellonella; however, its exposure to C. coronatus resulted in an increase in the activity to detectable level. In the case of C. vicina exposure to the fungus, the anti E. coli activity was significantly higher than in control larvae. The defense mechanisms of D. pini (species of economic importance in Europe) are presented for the first time. 相似文献
5.
Kerfoot SM Szczepanik M Tung JW Askenase PW 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(3):1717-1727
Contact sensitivity (CS) is related to delayed-type hypersensitivity and is a well-characterized prototype of T cell-mediated inflammation. However, the inflammatory response associated with CS is additionally dependent on Ag-specific IgM produced by a subpopulation of B cells in response to sensitization. Upon re-exposure to hapten, this IgM mediates rapid vascular activation and subsequent recruitment of proinflammatory T cells to the local site. Interference with this pathway prevents the full development of the classic delayed inflammatory response and is therefore termed the "CS initiation" pathway. In this study, we show that CS initiation is defective in mice deficient in activation-induced deaminase, an enzyme central to the process of somatic hypermutation. Using adoptive transfer experiments, we demonstrate that the defect is specific to a B-1-like population of B cells and that transfer of WT cells reconstitutes CS initiation mechanisms in deficient recipients. We went on to identify a novel subpopulation of Ag-binding B cells in the spleens of sensitized mice that possess initiation activity (CD19(+)CD5(+)Thy-1(int)IgM(high)IgD(high)) that we name "initiator B cells." Analysis of BCR H chain genes isolated from these cells revealed evidence of activation-induced deaminase-mediated somatic hypermutation. The sensitivity of CS initiation to very low amounts of sensitizing hapten suggests that the responsible B cells have increased IgM receptor gene mutations enabling selection to generate Abs with sufficient affinity to mediate the response. 相似文献
6.
Szczepanik W Dworniczek E Ciesiołka J Wrzesiński J Skala J Jezowska-Bojczuk M 《Journal of inorganic biochemistry》2003,94(4):355-364
The interactions of copper(II) complexes of kanamycin A with oxidation-susceptible biomolecules: 2'-deoxyguanosine, plasmid DNA and yeast tRNA(Phe) were studied in both the presence and absence of hydrogen peroxide. The mixture of complex with H(2)O(2) was found to be an efficient oxidant, converting dG to its 8-oxo derivative, generating strand breaks in plasmid DNA and multiple cleavages in tRNA(Phe). Some of these reactions may play a role in toxic effects of aminoglycoside antibiotics. These complexes were screened for their antibacterial activity. The microbiological studies undertaken to compare the bactericidal action of kanamycin A alone and complexed with copper(II) ions in both neutral and oxidative environment revealed that the enhancement of bactericidal action by Cu(II) was not statistically significant. 相似文献
7.
Energy metabolism in uncoupling protein 3 gene knockout mice 总被引:27,自引:0,他引:27
Vidal-Puig AJ Grujic D Zhang CY Hagen T Boss O Ido Y Szczepanik A Wade J Mootha V Cortright R Muoio DM Lowell BB 《The Journal of biological chemistry》2000,275(21):16258-16266
Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important roles in regulating energy expenditure, body weight, and thermoregulation. Other postulated roles for UCP3 include regulation of fatty acid metabolism, adaptive responses to acute exercise and starvation, and prevention of reactive oxygen species (ROS) formation. To address these questions, we have generated mice lacking UCP3 (UCP3 knockout (KO) mice). Here, we provide evidence that skeletal muscle mitochondria lacking UCP3 are more coupled (i.e. increased state 3/state 4 ratio), indicating that UCP3 has uncoupling activity. In addition, production of ROS is increased in mitochondria lacking UCP3. This study demonstrates that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS. Despite these effects on mitochondrial function, UCP3 does not seem to be required for body weight regulation, exercise tolerance, fatty acid oxidation, or cold-induced thermogenesis. The absence of such phenotypes in UCP3 KO mice could not be attributed to up-regulation of other UCP mRNAs. However, alternative compensatory mechanisms cannot be excluded. The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined. 相似文献
8.
The effect of pentoxifiline on post-injury hyperalgesia in rats and postoperative pain in patients 总被引:6,自引:0,他引:6
Wordliczek J Szczepanik AM Banach M Turchan J Zembala M Siedlar M Przewlocki R Serednicki W Przewlocka B 《Life sciences》2000,66(12):1155-1164
Recent studies demonstrate that activation of proinflammatory cytokines following injury intensifies the process of nociception. The present investigation assessed the influence of pre-injury pentoxifiline (PTFL, a non-specific cytokine inhibitor) on the development of post-injury nociception in animals and patients. It was established that intrathecal or intraperitoneal PTFL, elevated the nociceptive threshold for mechanical stimuli in the formalin test in rats. Pre-injury PTFL also inhibited pain-related behaviour. These findings correlate with a lower TNFalpha level in the serum of animals receiving pre-injury PTFL. In clinical investigations PTFL was administered intravenously before elective cholecystectomy. Patients who received preoperative PTFL had lower opioid requirements in the early postoperative period than control. At the same time, serum levels of TNFalpha and IL6 were lower in the PTFL group. Our results confirm the hypothesis as to the possibility of modulating of nociception through preemptive administration of a cytokine inhibitor. 相似文献
9.
Szczepanik W Kaczmarek P Jezowska-Bojczuk M 《Journal of inorganic biochemistry》2004,98(12):2141-2148
Actinomycin D (AD) is a potent anticancer drug widely applied in therapy, which however exhibits very high toxicity in humans. As the character of donors present in the AD molecule seems to be very favorable for Cu(II) ions, we undertook the coordination study on the Cu(II)-AD system. Potentiometric experiments proved a formation of very stable complexes and with the use of spectroscopic methods the identification of the binding sites was made. The values of potential energy minima, provided by theoretical modeling, confirmed the feasibility of formation of the complexes in water solution. We also demonstrated a significant effect of Cu(II) ions on AD interactions with DNA. The strand-nicking activity was observed. This process could be correlated with the speciation of complex forms. We also found out that in the presence of H2O2, low levels of Cu(II)-AD complexes induce the formation of considerable amounts of linearised plasmid. In consequence, the hypothesis is proposed that the physiologically available cupric ions may participate in the drug-induced toxic effects. 相似文献
10.
Krezel A Szczepanik W Swiatek M Jezowska-Bojczuk M 《Bioorganic & medicinal chemistry》2004,12(15):4075-4080
Aminoglycoside antibiotics constitute a class of the drugs of high interest, whose therapeutic action is based upon the electrostatic interaction with the variety of RNA molecules. The positive charge of these drugs molecules, located at their amino functions, has a prevailing influence on this process. The potentiometry and (1)H NMR spectroscopy are applied hereby to achieve the characteristics of the acid-base properties of particular protonating groups. We found that the pK values of deprotonation processes cover a wide values range 6-9.8. The correlation spectra of sisomicin, both COSY and TOCSY, allowed attributing unambiguously individual signals to the corresponding protons. These spectra involve a lot of the cross-peaks originating from the B and C rings protons, while the analogous signals originating from A rings protons are less numerous. Molecular modeling provided that the methylated amino group of A ring is located too far from the protonated functions of the remaining rings to affect their pK values. The phenomena observed herein are discussed in line of strength of the analogous processes observed for other aminoglycosides. As the result, four types of amino groups consisted within these antibiotics are distinguished. 相似文献