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51.
Scumpia PO Delano MJ Kelly KM O'Malley KA Efron PA McAuliffe PF Brusko T Ungaro R Barker T Wynn JL Atkinson MA Reeves WH Salzler MJ Moldawer LL 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(11):7943-7949
Regulatory T cells (Tregs), including natural CD4+CD25+ Tregs and inducible IL-10 producing T regulatory type 1 (T(R)1) cells, maintain tolerance and inhibit autoimmunity. Recently, increased percentages of Tregs have been observed in the blood of septic patients, and ex vivo-activated Tregs were shown to prevent polymicrobial sepsis mortality. Whether endogenous Tregs contribute to sepsis outcome remains unclear. Polymicrobial sepsis, induced by cecal ligation and puncture, caused an increased number of splenic Tregs compared with sham-treated mice. Splenic CD4+CD25+ T cells from septic mice expressed higher levels of Foxp3 mRNA and were more efficient suppressors of CD4+CD25- T effector cell proliferation. Isolated CD4+ T cells from septic mice displayed increased intracellular IL-10 staining following stimulation, indicating that T(R)1 cells may also be elevated in sepsis. Surprisingly, Ab depletion of total CD4+ or CD4+CD25+ populations did not affect mortality. Furthermore, no difference in survival outcome was found between CD25 or IL-10 null mice and wild-type littermates, indicating that Treg or T(R)1-generated IL-10 are not required for survival. These results demonstrate that, although sepsis causes a relative increase in Treg number and increases their suppressive function, their presence does not contribute significantly to overall survival in this model. 相似文献
52.
Novel lymphotoxin alpha (LTalpha) knockout mice with unperturbed tumor necrosis factor expression: reassessing LTalpha biological functions
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Liepinsh DJ Grivennikov SI Klarmann KD Lagarkova MA Drutskaya MS Lockett SJ Tessarollo L McAuliffe M Keller JR Kuprash DV Nedospasov SA 《Molecular and cellular biology》2006,26(11):4214-4225
Lymphotoxin alpha (LTalpha) can exist in soluble form and exert tumor necrosis factor (TNF)-like activity through TNF receptors. Based on the phenotypes of knockout (KO) mice, the physiological functions of LTalpha and TNF are considered partly redundant, in particular, in supporting the microarchitecture of the spleen and in host defense. We exploited Cre-LoxP technology to generate a novel neomycin resistance gene (neo) cassette-free LTalpha-deficient mouse strain (neo-free LTalpha KO [LTalphaDelta/Delta]). Unlike the "conventional" LTalpha-/- mice, new LTalphaDelta/Delta animals were capable of producing normal levels of systemic TNF upon lipopolysaccharide (LPS) challenge and were susceptible to LPS/D-galactosamine (D-GalN) toxicity. Activated neutrophils, monocytes, and macrophages from LTalphaDelta/Delta mice expressed TNF normally at both the mRNA and protein levels as opposed to conventional LTalpha KO mice, which showed substantial decreases in TNF. Additionally, the spleens of the neo-free LTalpha KO mice displayed several features resembling those of LTbeta KO mice rather than conventional LTalpha KO animals. The phenotype of the new LTalphaDelta/Delta mice indicates that LTalpha plays a smaller role in lymphoid organ maintenance than previously thought and has no direct role in the regulation of TNF expression. 相似文献
53.
Aidan Ryan Madeline Murphy Catherine Godson Fionnuala B. Hickey 《Apoptosis : an international journal on programmed cell death》2009,14(12):1435-1450
Since the early observation that similarities between thyroiditis and insulitis existed, the important role played by inflammation
in the development of diabetes has been appreciated. More recently, experiments have shown that inflammation also plays a
prominent role in the development of target organ damage arising as complications, with both elements of the innate and the
adaptive immune system being involved, and that cytokines contributing to local tissue damage may arise from both infiltrating
and resident cells. This review will discuss the experimental evidence that shows that inflammatory cell-mediated apoptosis
contributes to target organ damage, from beta cell destruction to both micro- and macro-vascular disease complications, and
also how alterations in leukocyte turnover affects immune function. 相似文献
54.
55.
Colvin GA Lambert JF Carlson JE McAuliffe CI Abedi M Quesenberry PJ 《In vitro cellular & developmental biology. Animal》2002,38(6):343-351
Space flight with associated microgravity is complicated by "astronaut's anemia" and other hematologic abnormalities. Altered erythroid differentiation, red cell survival, plasma volume, and progenitor numbers have been reported. We studied the impact of microgravity on engraftable stem cells, culturing marrow cells in rotary wall vessel (RWV) culture chambers mimicking microgravity and in normal gravity nonadherent Teflon bottles. A quantitative competitive engraftment technique was assessed under both conditions in lethally irradiated hosts. We assessed 8-wk engraftable stem cells over a period spanning at least one cell cycle for cytokine (FLT-3 ligand, thrombopoietin [TPO], steel factor)-activated marrow stem cells. Engraftable stem cells were supported out to 56 h under microgravity conditions, and this support was superior to that seen in normal-gravity Teflon bottle cultures out to 40 h, with Teflon bottle culture support superior to RWV from 40 to 56 h. A nadir of stem cell number was seen at 40 h in Teflon and 48 h in RWV, suggesting altered marrow stem cell cycle kinetics under microgravity. This is the first study of engraftable stem cells under microgravity conditions, and the differences between microgravity and normal gravity cultures may present opportunities for unique future stem cell expansion strategies. 相似文献
56.
Roger C. Harrison Charles A. McAuliffe Michael E. Friedman 《Inorganica chimica acta》1984,92(1):43-46
Toxicity data and some preliminary antitumor testing results are reported for the new complexes cis-PtLX2 (L = 1H-pyrrolo[2,3-b]pyridine, (7-azaindole); X2 = Cl2, I2 oxalate). Although these complexes have the cis-PtN2X2 configuration recognised as desirable for effective antitumor behavior, no significant antitumor properties were observed against a number of primary screens; although interesting toxicity differences were observed between the three compounds. 相似文献
57.
The facultative potentially tetradentate thioether ligands 1,2-bis(methylthioethylthio)ethane (2,2,2), 1,3-bis(2-methylthioethylthio)propane (2,3,2) and 1,2-bis(3-methylthiopropylthio)ethane (3,2,3) react with copper(II) salts to form Cu2(2,2,2)Cl4, Cu3(ligand)X6 (ligand = 2,3,2 and 3,2,3 X = Cl; ligand = 2,2,2 2,3,2 and 3,2,3 X = Br), and Cu(ligand)(ClO4)2. The stoichiometry and structures of these complexes are discussed in terms of the steric demands of the ligand and the nature of the halide. The [Cu(2,3,2)(ClO4)] ClO4 and [Cu(3,2,3)(ClO4) [ClO4 complexes have electronic spectra which exhibit the intense 600 nm band characteristic of the "blue" copper proteins. In fact, the spectrum of [Cu(2,3,2)(ClO4)]ClO4 is very similar to that of pseudomonas aeroginosa azurin. 相似文献
58.
Immunization of chickens by intravenous inoculation of preparations derived from blood infected with Plasmodium galinaceum led to reduced infectivity to mosquitoes (Aedes aegypti) during subsequently induced blood infection but had little effect on the course of asexual parasitemia. Immunization with preparations containing intracellular gametocytes was much less effective than immunization with preparations in which the extracellular gametes had been released during gametogenesis (emergence and exflagellation) prior to inoculation. By far the most effective material were preparations of partially purified gametes of both sexes. Three weekly inoculations of this material resulted in 99.99% suppression of infectivity to mosquitoes during subsequently induced blood infection. Preparations of purified gamete material from which gametes of one or another sex were absent were considerably less effective as transmission-blocking immunogens than the mixed gamete preparation. It is possible that the two sexes of gamete act synergistically to induce transmission-blocking immunity. 相似文献
59.
M.E. Friedman L. Chasteen R. Shaw S. Allen C.A. McAuliffe 《Chemico-biological interactions》1982,42(3):321-333
Fumarase (EC 4.2.1.2) and mitochondrial L-malate dehydrogenase (EC 1.1.1.37) were both inhibited by NaAuCl4 and KAuBr4. The inhibition for both was measured as a function of gold complex concentration and aquation time, and the NaAuCl4 inhibition was also measured in the presence of 0.15 M NaCl. Regeneration of the enzyme activity after NaAuCl4 inhibition using L-cysteine, L-methionine and NaCN was also investigated. Sodium dodecyl sulfate (SDS) acrylamide gel electrophoresis and amino acid analysis was performed on the NaAuCl4 inhibited enzymes as well as on ribonuclease A (EC 3.1.26.2), lysozyme (EC 3.2.1.17) and liver alcohol dehydrogenase (EC 1.1.1.1). It was observed that the inhibition was proportional to the gold complex concentration but decreased markedly after aquation of the complex. In the presence of NaCl the initial rate of inactivation is essentially unaffected unless the complex has been aquated and then the initial rate is increased. Gel electrophoresis on gold complex-enzyme mixtures show polymerization for ribonuclease and lysozyme and amino acid analysis indicates that no oxidation has taken place. From these results, a binding mechanism is postulated for the inhibition of the dehydrogenases by direct displacement of a halide ligand, probably by two groups on the enzyme, at least one of which may be a sulfur containing acid. 相似文献
60.
Human parainfluenza virus type 3 (PIV3) expressing the hemagglutinin protein of measles virus provides a potential method for immunization against measles virus and PIV3 in early infancy
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Durbin AP Skiadopoulos MH McAuliffe JM Riggs JM Surman SR Collins PL Murphy BR 《Journal of virology》2000,74(15):6821-6831