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71.
The apoptotic and proliferative fate of cytokine-induced killer cells after redirection to tumor cells with bispecific Ab 总被引:6,自引:0,他引:6
BACKGROUND: Cytokine-induced killer (CIK) cells are ex vivo expanded T cells with co-expression of CD3 and CD56 and NK activity. They have recently been evaluated in a phase I/II clinical trial against malignant lymphoma. Bispecific Ab (bsAb) redirect CIK cells to tumor targets, thus enhancing their cytotoxicity. While bsAb may improve T-cell mediated anti-tumor activity, little is known about the fate of effector cells upon redirection to tumor targets using a bsAb. METHODS: Using ex vivo-activated CIK cells, Her2/neu expressing breast and ovarian cell lines and a F(ab')2 Her2/neu x CD3 bsAb, we investigated the anti-tumor activity and the proliferative and apoptotic outcome of CIK cells. RESULTS: When redirected to tumor targets with bsAb, there was a significant increase in anti-tumor activity as well as an increase in both CIK cell proliferation and apoptosis. The addition of agonistic Ab against CD28 did not significantly increase proliferation or apoptosis of CIK cells redirected to CD80- and CD86- tumor targets. To attempt to reduce T-cell apoptosis, we incubated CIK cells in the presence of the pan-caspase inhibitor z-VAD-fmk, which led to a partial reduction in T-cell apoptosis without increasing cellular cytotoxicity. DISCUSSION: bsAb are effective in redirecting activated T cells to tumor targets and such redirection leads to both T-cell proliferation and apoptosis that are not altered by co-stimulation through CD28. Effector cell apoptosis can be reduced by using a caspase inhibitor but this does not increase CIK cell cytotoxicity. 相似文献
72.
Immunological reactions have a key role in health and disease and are complex events characterized by coordinated cell trafficking to specific locations throughout the body. Clarification of these cell-trafficking events is crucial for improving our understanding of how immune reactions are initiated, controlled and recalled. As we discuss here, an emerging modality for revealing cell trafficking is bioluminescence imaging, which harnesses the light-emitting properties of enzymes such as luciferase for quantification of cells and uses low-light imaging systems. This strategy could be useful for the study of a wide range of biological processes, such as the pathophysiology of graft-versus-host and graft-versus-leukaemia reactions. 相似文献
73.
Marie-Therese Lingitz Gregor Wollner Jonas Bauer Hannes Kuehtreiber Michael Mildner Dragan Copic Daniel Bormann Martin Direder Claus Georg Krenn Thomas Haider Lukas Leopold Negrin Hendrik jan Ankersmit 《Journal of cellular and molecular medicine》2023,27(13):1859-1866
Trauma represents one of the leading causes of death worldwide. Traumatic injuries elicit a dynamic inflammatory response with systemic release of inflammatory cytokines. Disbalance of this response can lead to systemic inflammatory response syndrome or compensatory anti-inflammatory response syndrome. As neutrophils play a major role in innate immune defence and are crucial in the injury-induced immunological response, we aimed to investigate systemic neutrophil-derived immunomodulators in trauma patients. Therefore, serum levels of neutrophil elastase (NE), myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) were quantified in patients with injury severity scores above 15. Additionally, leukocyte, platelet, fibrinogen and CRP levels were assessed. Lastly, we analysed the association of neutrophil-derived factors with clinical severity scoring systems. Although the release of MPO, NE and CitH3 was not predictive of mortality, we found a remarkable increase in MPO and NE in trauma patients as compared with healthy controls. We also found significantly increased levels of MPO and NE on Days 1 and 5 after initial trauma in critically injured patients. Taken together, our data suggest a role for neutrophil activation in trauma. Targeting exacerbated neutrophil activation might represent a new therapeutic option for critically injured patients. 相似文献
74.
Phylogenetic analysis of the 90 kD heat shock family of protein sequences and an examination of the relationship among animals, plants, and fungi species 总被引:17,自引:1,他引:16
The heat shock protein (Hsp) sequences, because of their ubiquity and high
degree of conservation, provide useful models for phylogenetic analysis. In
this paper I have carried out a global alignment of all available sequences
(a total of 31) for the 90-kD heat shock protein (Hsp90) family. The
minimum amino acid identity that is seen between presently known Hsp90
homologs is about 40% over the entire length, indicating that it is a
highly conserved protein. Based on the alignment, a number of signature
sequences that either are distinctive of the Hsp90 family or that
distinguish between the cytosolic and the endoplasmic reticular forms of
Hsp90 have been identified. Detailed phylogenetic analyses based on Hsp90
sequences reported here strongly indicate that the cytosolic and the
endoplasmic reticulum (ER) resident forms of Hsp90 constitute paralogous
gene families which arose by a gene duplication event that took place very
early in the evolution of eukaryotic cells. A minimum of two additional
gene duplication events, which took place at a later time, are required to
explain the presence of two different forms of Hsp90 that are found in
fungi and vertebrate species. In a consensus neighbor-joining bootstrap
tree based on Hsp90 sequences, plants and animals species grouped together
989 times of 1,000 (a highly significant score), indicating a closer
relationship between them as compared to fungi. A closer affiliation of
plant and animal species was also observed in the maximum-parsimony tree,
although the relationship was not significantly supported by this method. A
survey of the recent literature on this subject indicates that depending on
the protein sequence and the methods of phylogenetic analysis, the animal
species are indicated as closer relatives to either plants or fungi with
significant statistical support for both topologies. Thus the relationship
among the animal, plant, and fungi kingdoms remains an unresolved issue at
the present time.
相似文献
75.
The phylogenetic position of the archaebacteria and the place of eukaryotes
in the history of life remain a question of debate. Recent studies based on
some protein-sequence data have obtained unusual phylogenies for these
organisms. We therefore collected the protein sequences that were available
with representatives from each of the major forms of life: the
gram-negative bacteria, gram-positive bacteria, archaebacteria, and
eukaryotes. Monophyletic, unrooted phylogenies based on these sequence data
show that seven of 24 proteins yield a significant
gram-positive-archaebacteria clade/gram-negative- eukaryotic clade. The
phylogenies for these seven proteins cannot be explained by the traditional
three-way split of the eukaryotes, archaebacteria, and eubacteria. Nine of
the 24 proteins yield the traditional gram-positive-gram-negative
clade/archaebacteria-eukaryotic clade. The remaining eight proteins give
phylogenies that cannot be statistically distinguished. These results
support the hypothesis of a chimeric origin for the eukaryotic cell nucleus
formed from the fusion of an archaebacteria and a gram-negative bacteria.
相似文献
76.
S. Nishanth Kumar C Mohandas Bala Nambisan RS Sreerag CA Jayaprakas 《Folia microbiologica》2014,59(3):197-202
In continuation of our search for new antimicrobial secondary metabolites from Bacillus cereus associated with rhabditid entomopathogenic nematode, a new microbial diketopiperazine, cyclo(l-Pro-d-Arg), was isolated from the ethyl acetate extract of fermented modified nutrient broth. The chemical structures of the isolated compounds were identified based on their 1D, 2D NMR and high-resolution electrospray ionisation–mass spectroscopy data. Antibacterial activity of the compound was determined by minimum inhibitory concentration and disc diffusion method against medically important bacteria, and the compound was recorded to have significant antibacterial activity against test bacteria. The highest activity was recorded against Klebsiella pneumoniae (1 μg/mL). Cyclo(l-Pro-d-Arg) was recorded to have significant antitumor activity against HeLa cells (IC50 value 50 μg/mL), and this compound was recorded to have no cytotoxicity against normal monkey kidney cells (VERO) up to 100 μg/mL). To the best of our knowledge, this is the first time that cyclo(l-Pro-d-Arg) has been isolated from a microbial natural source. 相似文献
77.
We used immunohistochemistry to quantify and compare the expression of Toll-like receptor 2 (TLR2) and cluster of differentiation 14 (CD14) in gingival tissues of both healthy individuals and patients with chronic periodontitis. We also correlated the expression of TLR2 and CD14 with the histological grades of chronic periodontitis. We examined 30 gingival specimens from chronic periodontitis patients and 10 from healthy individuals. Tissues from both groups were immunostained with antibodies against TLR2 and CD14. TLR2 and CD14 were expressed by endothelial cells, fibroblasts, lymphocytes and plasma cells. The immunohistochemical expression of TLR2 and CD14 was significantly greater in inflammatory cells of the chronic periodontitis group than in healthy individuals. Expression of these molecules was greater in the inflammatory cells of connective tissue adjacent to pocket epithelium in both groups. The expression of TLR2 and CD14 was greatest in the periodontitis group that was classified as severe grade, followed by moderate and mild grades, which suggests a role of TLR2 and CD14 in the pathogenesis of chronic periodontitis. The positive correlation of TLR2 and CD14 expression levels with the severity grades of chronic periodontitis suggests that they are correlated also with disease severity; therefore, they may be useful for predicting disease progression. Our findings are consistent with the possibility that CD14 acts as a co-receptor for TLR2. 相似文献
78.
79.
AAM Coelho-Castelo AP Trombone RS Rosada RR Santos Jr VLD Bonato A Sartori CL Silva 《Genetic vaccines and therapy》2006,4(1):1-10
In order to assess a new strategy of DNA vaccine for a more complete understanding of its action in immune response, it is important to determine the in vivo biodistribution fate and antigen expression. In previous studies, our group focused on the prophylactic and therapeutic use of a plasmid DNA encoding the Mycobacterium leprae 65-kDa heat shock protein (Hsp65) and achieved an efficient immune response induction as well as protection against virulent M. tuberculosis challenge. In the present study, we examined in vivo tissue distribution of naked DNA-Hsp65 vaccine, the Hsp65 message, genome integration and methylation status of plasmid DNA. The DNA-Hsp65 was detectable in several tissue types, indicating that DNA-Hsp65 disseminates widely throughout the body. The biodistribution was dose-dependent. In contrast, RT-PCR detected the Hsp65 message for at least 15 days in muscle or liver tissue from immunized mice. We also analyzed the methylation status and integration of the injected plasmid DNA into the host cellular genome. The bacterial methylation pattern persisted for at least 6 months, indicating that the plasmid DNA-Hsp65 does not replicate in mammalian tissue, and Southern blot analysis showed that plasmid DNA was not integrated. These results have important implications for the use of DNA-Hsp65 vaccine in a clinical setting and open new perspectives for DNA vaccines and new considerations about the inoculation site and delivery system. 相似文献
80.