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31.
32.
A fatal cytokine-induced systemic inflammatory response reveals a critical role for NK cells 总被引:5,自引:0,他引:5
Carson WE Yu H Dierksheide J Pfeffer K Bouchard P Clark R Durbin J Baldwin AS Peschon J Johnson PR Ku G Baumann H Caligiuri MA 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(8):4943-4951
The mechanism of cytokine-induced shock remains poorly understood. The combination of IL-2 and IL-12 has synergistic antitumor activity in vivo, yet has been associated with significant toxicity. We examined the effects of IL-2 plus IL-12 in a murine model and found that the daily, simultaneous administration of IL-2 and IL-12 resulted in shock and 100% mortality within 4 to 12 days depending on the strain employed. Mice treated with IL-2 plus IL-12 exhibited NK cell apoptosis, pulmonary edema, degenerative lesions of the gastrointestinal tract, and elevated serum levels of proinflammatory cytokines and acute phase reactants. The actions of TNF-alpha, IFN-gamma, macrophage-inflammatory protein-1alpha, IL-1, IL-1-converting enzyme, Fas, perforin, inducible nitric oxide synthase, and STAT1 did not contribute to the observed toxicity, nor did B or T cells. However, toxicity and death from treatment with IL-2 plus IL-12 could be completely abrogated by elimination of NK cells. These results suggest that the fatal systemic inflammatory response induced by this cytokine treatment is critically dependent upon NK cells, but does not appear to be mediated by the known effector molecules of this cellular compartment. These data may provide insight into the pathogenesis of cytokine-induced shock in humans. 相似文献
33.
TNF and lymphotoxin beta cooperate in the maintenance of secondary lymphoid tissue microarchitecture but not in the development of lymph nodes 总被引:3,自引:0,他引:3
Kuprash DV Alimzhanov MB Tumanov AV Anderson AO Pfeffer K Nedospasov SA 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(12):6575-6580
Inactivation of genes encoding members of TNF and TNF receptor families reveal their divergent roles in the formation and function of secondary lymphoid organs. Most lymphotoxin alpha (ltalpha)- and all lymphotoxin beta receptor (ltbetar)-deficient mice are completely devoid of lymph nodes (LNs); however, most lymphotoxin beta (ltbeta)-deficient mice develop mesenteric LNs. Tnf- and tnfrp55-deficient mice develop a complete set of LNs, while ltbeta/tnfrp55 double-deficient mice lack all LNs, demonstrating cooperation between LTbeta and TNFRp55 in LN development. Now we report that ltbeta/tnf double-deficient mice develop the same set of mucosal LNs as do ltbeta-deficient mice, suggesting that ligands other than TNF signal through TNFRp55 during LN development. These LNs retain distinct T and B cells areas; however, they lack follicular dendritic cell networks. Structures resembling germinal centers can be found in the LNs from immunized ltbeta-deficient mice but not in ltbeta/tnf double-deficient mice. Additionally, stromal components of the spleen and LNs appear to be more severely disturbed in ltbeta/tnf double-deficient mice as compared with ltbeta-deficient mice. We conclude that LTbeta and TNF cooperate in the establishment of the correct microarchitecture of lymphoid organs. 相似文献
34.
Rab9 GTPase regulates late endosome size and requires effector interaction for its stability 总被引:1,自引:0,他引:1
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Rab9 GTPase resides in a late endosome microdomain together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47 kDa (TIP47). To explore the importance of Rab9 for microdomain establishment, we depleted the protein from cultured cells. Rab9 depletion decreased late endosome size and reduced the numbers of multilamellar and dense-tubule-containing late endosomes/lysosomes, but not multivesicular endosomes. The remaining late endosomes and lysosomes were more tightly clustered near the nucleus, implicating Rab9 in endosome localization. Cells displayed increased surface MPRs and lysosome-associated membrane protein 1. In addition, cells showed increased MPR synthesis in conjunction with MPR missorting to the lysosome. Surprisingly, Rab9 stability on late endosomes required interaction with TIP47. Rabs are thought of as independent, prenylated entities that reside either on membranes or in cytosol, bound to GDP dissociation inhibitor. These data show that Rab9 stability is strongly influenced by a specific effector interaction. Moreover, Rab9 and the proteins with which it interacts seem critical for the maintenance of specific late endocytic compartments and endosome/lysosome localization. 相似文献
35.
36.
Inhibition of natural killer cells results in acceptance of cardiac allografts in CD28-/- mice 总被引:9,自引:0,他引:9
Maier S Tertilt C Chambron N Gerauer K Hüser N Heidecke CD Pfeffer K 《Nature medicine》2001,7(5):557-562
Successful transplantation of allogeneic organs is an important objective in modern medicine. However, sophisticated immune defense mechanisms, primarily evolved to combat infections, often work against medical transplantation. To investigate the roles of natural and adaptive immune responses in transplant rejection, we functionally inactivated key effector systems of the innate (NK cells) and the adaptive immune system (CD28-mediated costimulation of T cells) in mice. Neither of these interventions alone led to acceptance of allogeneic vascularized cardiac grafts. In contrast, inhibition of NK-receptor-bearing cells combined with CD28-costimulation blockade established long-term graft acceptance. These results indicate a concerted interplay between innate and adaptive immune surveillance for graft rejection. Thus we suggest that inactivation of NK-receptor-bearing cells could be a new strategy for successful survival of solid-organ transplants. 相似文献
37.
(13)C-NMR analyses of Cantharellus cibarius growth media were performed. We found exudation of trehalose and mannitol, which may explain the phenomenon of reproducing Pseudomonas bacteria observed inside fruit bodies. Exudation varied with strain and environment. NMR analyses of stored (13)C was also performed. Trehalose, mannitol, and arginine were revealed. The mannitol pathway seems to play an important role for trehalose production in this species. This is the first study of the fate of the photosynthetically derived carbon in the highly appreciated edible ectomycorrhizal mushroom Cantharellus cibarius. 相似文献
38.
Allan J. Canty Jim PatelMichel Pfeffer Brian W. SkeltonAllan H. White 《Inorganica chimica acta》2002,327(1):20-25
Neutral palladium(IV) complexes containing the bis(pyrazol-1-yl)borate ligand, PdMe3{(pz)2BH2}(L) [L=py-d5 (4), PMe2Ph (6)], are generated in solution by oxidative addition of iodomethane to [PdMe2{(pz)2BH2}]− at −70 °C followed by addition of L; the Pd(IV) complexes reductively eliminate ethane above 0 °C. Stable Pt(IV) analogues of 4 and 6 have been isolated, and comparison of NMR spectra for Pd(IV) and Pt(IV) species support structural assignments for the unstable Pd(IV) complexes. The complex PtMe3{(pz)2BH2}(py) (1a) has been characterised by X-ray diffraction, together with Pt(mq)Me2{(pz)2BH2} (2) (mq=8-methylquinolinyl); both complexes show a fac-PtC3 configuration for Pt(IV), and for 2 the PtN distances are ∼0.03 Å shorter than in the isostructural Pd(IV) complex. 相似文献
39.
P0 of beet Western yellows virus is a suppressor of posttranscriptional gene silencing 总被引:9,自引:0,他引:9
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Pfeffer S Dunoyer P Heim F Richards KE Jonard G Ziegler-Graff V 《Journal of virology》2002,76(13):6815-6824
40.
Redundancy in tumor necrosis factor (TNF) and lymphotoxin (LT) signaling in vivo: mice with inactivation of the entire TNF/LT locus versus single-knockout mice
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Kuprash DV Alimzhanov MB Tumanov AV Grivennikov SI Shakhov AN Drutskaya LN Marino MW Turetskaya RL Anderson AO Rajewsky K Pfeffer K Nedospasov SA 《Molecular and cellular biology》2002,22(24):8626-8634
Homologous genes and gene products often have redundant physiological functions. Members of the tumor necrosis factor (TNF) family of cytokines can signal activation, proliferation, differentiation, costimulation, inhibition, or cell death, depending on the type and status of the target cell. TNF, lymphotoxin alpha (LTalpha), and LTbeta form a subfamily of a larger family of TNF-related ligands with their genes being linked within a compact 12-kb cluster inside the major histocompatibility complex locus. Singly TNF-, LTalpha-, and LTbeta-deficient mice share several phenotypic features, suggesting that TNF/LT signaling pathways may regulate overlapping sets of target genes. In order to directly address the issue of redundancy of TNF/LT signaling, we used the Cre-loxP recombination system to create mice with a deletion of the entire TNF/LT locus. Mice with a triple LTbeta/TNF/LTalpha deficiency essentially manifest a combination of LT and TNF single-knockout phenotypes, except for microarchitecture of the spleen, where the disorder of lymphoid cell positioning and functional T- and B-cell compartmentalization is severer than that found in TNF or LT single-knockout mice. Thus, our data support the notion that TNF and LT have largely nonredundant functions in vivo. 相似文献