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Macrophage clearance of dying cells is of crucial importance to maintain tissue homeostasis. Here, we show that brief treatment (15min) of Jurkat T cells with agonistic anti-Fas antibodies or recombinant Fas ligand results in efficient phagocytosis by human monocyte-derived macrophages prior to the occurrence of common biomarkers of apoptosis. Similar findings were obtained when using primary human T cells. Macrophage engulfment of pre-apoptotic target cells was suppressed in the absence of serum. Moreover, pre-apoptotic cells secreted annexin I and administration of Boc1, a formyl peptide receptor/lipoxin receptor antagonist markedly attenuated their engulfment. Finally, pre-apoptotic Jurkat cells induced lower macrophage production of tumor necrosis factor-alpha and higher production of interleukin-10 in comparison to apoptotic target cells. 相似文献
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Cappenberg Thom E. Hordijk Kees A. Jonkheer Gert J. Lauwen Jos P. M. 《Hydrobiologia》1982,91(1):161-168
The turnover and exchange rates, as well as the diffusion processes, concerning the input and output of carbon compounds at
the mud-water interface, were studied. The carbon input rates were derived from the annual sedimentation rates of particulate
organic matter (about 1 100 kg C · yr−1). The nature of the sedimented POC, and its breakdown pathways and turnover rates towards important metabolic intermediates
in methanogenesis, were examined. The breakdown kinetics ofChlorella cell walls, a dominant green alga in Lake Vechten, was studied using U-14C-labelled cell walls. The breakdown of the cell walls appears to the rate-limiting step in anaerobic mineralization.
Using first order kinetic equations, and HPLC and GLC and radio-chemical methods, turnover rate constants (k-values) of between
0.18 and 0.32 day−1 and pool sizes of algal cell walls of 37 to 80 μg · g−1 wet mud were found, giving turnover rates of 7.7 to 25.6 μg · g−1 · day−1 of cell wall material. The turnover rates (k-values between 0.07 and 0.31 h−1) of acetate, the most important breakdown product, and its concentration gradients (between 5 and 30 μmol) and diffusion
coefficient (Ds = 2.2 × 10−6 cm2 · s−1) just in and above mud-water interface, was quantified. The diffusion of acetate, within the sediments, could not account
for the turnover rates observed.
Finally, from acetate flux data and from those on the rates of formation of carbon dioxide and methane, the output of carbon
and its cycling in Lake Vechten are discussed. 相似文献
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MHC II in Dendritic Cells is Targeted to Lysosomes or T Cell-Induced Exosomes Via Distinct Multivesicular Body Pathways 总被引:1,自引:0,他引:1
Sonja I. Buschow Esther N. M. Nolte-'t Hoen Guillaume van Niel Maaike S. Pols Toine ten Broeke Marjolein Lauwen Ferry Ossendorp Cornelis J. M. Melief Graça Raposo Richard Wubbolts Marca H. M. Wauben Willem Stoorvogel 《Traffic (Copenhagen, Denmark)》2009,10(10):1528-1542
Dendritic cells (DCs) express major histocompatibility complex class II (MHC II) to present peptide antigens to T cells. In immature DCs, which bear low cell surface levels of MHC II, peptide-loaded MHC II is ubiquitinated. Ubiquitination drives the endocytosis and sorting of MHC II to the luminal vesicles of multivesicular bodies (MVBs) for lysosomal degradation. Ubiquitination of MHC II is abrogated in activated DCs, resulting in an increased cell surface expression. We here provide evidence for an alternative MVB sorting mechanism for MHC II in antigen-loaded DCs, which is triggered by cognately interacting antigen-specific CD4+ T cells. At these conditions, DCs generate MVBs with MHC II and CD9 carrying luminal vesicles that are secreted as exosomes and transferred to the interacting T cells. Sorting of MHC II into exosomes was, in contrast to lysosomal targeting, independent of MHC II ubiquitination but rather correlated with its incorporation into CD9 containing detergent-resistant membranes. Together, these data indicate two distinct MVB pathways: one for lysosomal targeting and the other for exosome secretion. 相似文献
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W van den Brink C van der Loos H Volkers R Lauwen F van den Berg H J Houthoff P K Das 《The journal of histochemistry and cytochemistry》1990,38(3):325-329
A combination of beta-galactosidase enzyme and the immunogold/silver staining method was studied for evaluation of double-staining experiments. Applications are shown for immunohistochemical double staining using two monoclonal antibodies and for combined immunohistochemistry and DNA in situ hybridization in one tissue section. The following advantages for the present double-staining method were evaluated: superior sensitivity of the immunogold/silver staining method for at least one epitope, which also allows detection of biotinylated DNA probes. The structure of the indolyl precipitate after revelation of beta-galactosidase activity did not show a concealing effect during a sequential double-staining method, as compared with the visualization of peroxidase with diaminobenzidine. These factors, and the sharply contrasting colored reaction products of beta-galactosidase (blue-green) and the immunogold/silver staining method including silver enhancement (brown-black), allow clear distinction of mixed-stained cell constituents. 相似文献
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Bos R van Duikeren S van Hall T Lauwen MM Parrington M Berinstein NL McNeil B Melief CJ Verbeek JS van der Burg SH Offringa R 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(9):6115-6122
Avipoxvirus-based vectors, such as recombinant canarypox virus ALVAC, are studied extensively as delivery vehicles for vaccines against cancer and infectious diseases. Effective use of such vaccines is expected to benefit from proper understanding of the interaction between these viral vectors and the host immune system. We performed preclinical vaccination experiments in a murine tumor model to analyze the immunogenic properties of an ALVAC-based vaccine against carcinoembryonic Ag (ALVAC-CEA), a tumor-associated autoantigen commonly overexpressed in colorectal cancers. The protective CEA-specific immunity induced by this vaccine consisted of CD4(+) T cell responses with a mixed Th1/Th2 cytokine profile that were accompanied by potent humoral responses, but not by CEA-specific CD8(+) CTL immunity. In contrast, protective immunity induced by a CEA-specific DNA vaccine (DNA-CEA) consisted of Th1 and CTL responses. Modification of the ALVAC-CEA vaccine through coinjection of DNA-CEA, admixture with CpG oligodeoxynucleotides, or supplementation with additional transgenes encoding a triad of costimulatory molecules (TRICOM) did not result in induction of CEA-specific CTL responses. Even though these results suggested that ALVAC does not elicit Ag-specific CTLs, immunization with ALVAC vaccines against other Ags efficiently induced CTL responses. Our data show that the capacity of ALVAC vaccines to elicit CTL immunity against transgene-encoded Ags critically depends on the presence of highly immunogenic CTL epitopes in these Ags. This consideration needs to be taken into account with respect to the design and evaluation of vaccination strategies that use ALVAC-based vaccine. 相似文献
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Pierre Theurey Niamh M. C. Connolly Ilaria Fortunati Emy Basso Susette Lauwen Camilla Ferrante Catarina Moreira Pinho Alvin Joselin Anna Gioran Daniele Bano David S. Park Maria Ankarcrona Paola Pizzo Jochen H. M. Prehn 《Aging cell》2019,18(3)
Mitochondrial dysfunction is implicated in most neurodegenerative diseases, including Alzheimer's disease (AD). We here combined experimental and computational approaches to investigate mitochondrial health and bioenergetic function in neurons from a double transgenic animal model of AD (PS2APP/B6.152H). Experiments in primary cortical neurons demonstrated that AD neurons had reduced mitochondrial respiratory capacity. Interestingly, the computational model predicted that this mitochondrial bioenergetic phenotype could not be explained by any defect in the mitochondrial respiratory chain (RC), but could be closely resembled by a simulated impairment in the mitochondrial NADH flux. Further computational analysis predicted that such an impairment would reduce levels of mitochondrial NADH, both in the resting state and following pharmacological manipulation of the RC. To validate these predictions, we utilized fluorescence lifetime imaging microscopy (FLIM) and autofluorescence imaging and confirmed that transgenic AD neurons had reduced mitochondrial NAD(P)H levels at rest, and impaired power of mitochondrial NAD(P)H production. Of note, FLIM measurements also highlighted reduced cytosolic NAD(P)H in these cells, and extracellular acidification experiments showed an impaired glycolytic flux. The impaired glycolytic flux was identified to be responsible for the observed mitochondrial hypometabolism, since bypassing glycolysis with pyruvate restored mitochondrial health. This study highlights the benefits of a systems biology approach when investigating complex, nonintuitive molecular processes such as mitochondrial bioenergetics, and indicates that primary cortical neurons from a transgenic AD model have reduced glycolytic flux, leading to reduced cytosolic and mitochondrial NAD(P)H and reduced mitochondrial respiratory capacity. 相似文献
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