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Dahlke K Wrann CD Sommerfeld O Sossdorf M Recknagel P Sachse S Winter SW Klos A Stahl GL Ma YX Claus RA Reinhart K Bauer M Riedemann NC 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(5):3066-3075
Complement activation represents a crucial innate defense mechanism to invading microorganisms, but there is an eminent lack of understanding of the separate contribution of the different complement activation pathways to the host response during sepsis. We therefore investigated different innate host immune responses during cecal ligation and puncture (CLP)-induced sepsis in mice lacking either the alternative (fD(-/-)) or classical (C1q(-/-)) complement activation pathway. Both knockout mice strains showed a significantly reduced survival and increased organ dysfunction when compared with control mice. Surprisingly, fD(-/-) mice demonstrated a compensated bacterial clearance capacity as control mice at 6 h post CLP, whereas C1q(-/-) mice were already overwhelmed by bacterial growth at this time point. Interestingly, at 24 h after CLP, fD(-/-) mice failed to clear bacteria in a way comparable to control mice. However, both knockout mice strains showed compromised C3 cleavage during sepsis. Investigating potential causes for this discrepancy, we were able to demonstrate that despite normal bacterial clearance capacity early during the onset of sepsis, fD(-/-) mice displayed increased inflammatory cytokine generation and neutrophil recruitment into lungs and blood when compared with both control- and C1q(-/-) mice, indicating a potential loss of control over these immune responses. Further in vitro experiments revealed a strongly increased Nf-κB activation capacity in isolated neutrophils from fD(-/-) mice, supporting this hypothesis. Our results provide evidence for the new concept that the alternative complement activation pathway exerts a distinctly different contribution to the innate host response during sepsis when compared with the classical pathway. 相似文献
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Priscila R Moreira Marcos A Maioli Hyllana CD Medeiros Marieli Guelfi Flávia TV Pereira Fábio E Mingatto 《Biological research》2014,47(1)
Background
The liver is an important organ for its ability to transform xenobiotics, making the liver tissue a prime target for toxic substances. The carotenoid bixin present in annatto is an antioxidant that can protect cells and tissues against the deleterious effects of free radicals. In this study, we evaluated the protective effect of bixin on liver damage induced by carbon tetrachloride (CCl4) in rats.Results
The animals were divided into four groups with six rats in each group. CCl4 (0.125 mL kg-1 body wt.) was injected intraperitoneally, and bixin (5.0 mg kg-1 body wt.) was given by gavage 7 days before the CCl4 injection. Bixin prevented the liver damage caused by CCl4, as noted by the significant decrease in serum aminotransferases release. Bixin protected the liver against the oxidizing effects of CCl4 by preventing a decrease in glutathione reductase activity and the levels of reduced glutathione and NADPH. The peroxidation of membrane lipids and histopathological damage of the liver was significantly prevented by bixin treatment.Conclusion
Therefore, we can conclude that the protective effect of bixin against hepatotoxicity induced by CCl4 is related to the antioxidant activity of the compound. 相似文献15.
Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-beta gene family. 总被引:29,自引:1,他引:28
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R de Martin B Haendler R Hofer-Warbinek H Gaugitsch M Wrann H Schlüsener J M Seifert S Bodmer A Fontana E Hofer 《The EMBO journal》1987,6(12):3673-3677
Human glioblastoma cells secrete a peptide, termed glioblastoma-derived T cell suppressor factor (G-TsF), which has suppressive effects on interleukin-2-dependent T cell growth. As shown here, complementary DNA for G-TsF reveals that G-TsF shares 71% amino acid homology with transforming growth factor-beta (TGF-beta). In analogy to TGF-beta it is apparently synthesized as the carboxy-terminal end of a precursor polypeptide which undergoes proteolytic cleavage to yield the 112 amino-acid-long mature form of G-TsF. Comparison of the amino-terminal sequence of G-TsF with that of porcine TGF-beta 2 and bovine cartilage-inducing factor B shows complete homology, which indicates that we have cloned the human analogue of these factors. It is tempting to consider a role for G-TsF in tumor growth where it may enhance tumor cell proliferation in an autocrine way and/or reduce immunosurveillance of tumor development. 相似文献
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Michael Wrann 《Biochemical and biophysical research communications》1978,84(1):269-274
Fibronectin was isolated from pooled human plasma by affinity chromatography on Sepharose-coupled gelatin and subjected to methylation analysis. The results indicate that the carbohydrate chains in fibronectin are very similar to those found in other serum glycoproteins, i.e. a common inner core structure consisting of two N-acetylglucosamine and three mannose residues attached to the polypeptide backbone via a N-acetylglucosamine-asparagine linkage. To this inner core are attached two side chains made up of N-acetylglucosamine, galactose and terminated by sialic acid. 相似文献
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Spexin is novel biomarker, which plays a potential role in glucose and lipid metabolisms. However, there was paucity of serum spexin levels in obesity and diabetes mellitus subjects. Hence the current study was aimed to find the relationship between the serum spexin levels in type 2 Diabetes mellitus (type 2 DM) with extrapolation of cardiovascular disease (CVD) risk. A cross-sectional study included 330 participants, subdivided as control (n=110), type 2 DM (n=110) and type 2 DM with CVD groups (n=110). HbA1c, insulin, lipid profile, spexin & leptin including blood pressure and body mass index were analyzed from all the participants. The serum spexin levels (ng/ml) were significantly decreased in type 2 DM (mean ± sd: 0.65 ± 0.03) and type 2 DM with CVD (0.48 ± 0.02) groups compared to the control (0.79 ± 0.03) group (p<0.001). The decreased spexin levels were observed in type 2 DM, and further more decreased in type 2 DM with CVD patients compared to controls indicating that spexin levels could be served as an early prediction of obesity-induced T2DM with CVD risk. 相似文献
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JR Abney CD Meliza B Cutler M Kingma JE Lochner BA Scalettar 《Biophysical journal》1999,77(5):2887-2895
Secretory granules containing a hybrid protein consisting of the regulated secretory protein tissue plasminogen activator and an enhanced form of green fluorescent protein were tracked at high spatial resolution in growth cones of differentiated PC12 cells. Tracking shows that granules, unlike synaptic vesicles, generally are mobile in growth cones. Quantitative analysis of trajectories generated by granules revealed two dominant modes of motion: diffusive and directed. Diffusive motion was observed primarily in central and peripheral parts of growth cones, where most granules diffused two to four orders of magnitude more slowly than comparably sized spheres in dilute solution. Directed motion was observed primarily in proximal parts of growth cones, where a subset of granules underwent rapid, directed motion at average speeds comparable to those observed for granules in neurites. This high-resolution view of the dynamics of secretory granules in growth cones provides insight into granule organization and release at nerve terminals. In particular, the mobility of granules suggests that granules, unlike synaptic vesicles, are not tethered stably to cytoskeletal structures in nerve terminals. Moreover, the slow diffusive nature of this mobility suggests that secretory responses involving centrally distributed granules in growth cones will occur slowly, on a time scale of minutes or longer. 相似文献
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Trace metal (Zn, Pb, Cu, Cr and Cd) concentrations in the water column and in the liver, muscle and gill tissues of Parachanna obscura and Clarias gariepinus in Agulu Lake, Nigeria, were investigated in June 2014 and compared with WHO and FAO safe limits for water and fish. Hazard index (HI) values were estimated to assess the potential public health risk of consuming contaminated fish. Lead and cadmium exceeded WHO guideline values for drinking water. In most cases, variations in concentration of the metals in organs were liver > muscle > gill. Differences in tissue-specific concentrations between species were not significant, except for zinc in muscles and gills. Cadmium and chromium were not detected in the fish, but lead was above the FAO maximum value for consumption. Hazard index values were below 1, indicating a low risk to public health. However, trace metal contamination in Agulu Lake is increasing. 相似文献
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