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Killing Mechanisms (killing + mechanism)
Selected AbstractsMicroReview: Competence-induced fratricide in streptococciMOLECULAR MICROBIOLOGY, Issue 6 2007Jean-Pierre Claverys Summary Competence for natural genetic transformation in Streptococcus pneumoniae is controlled by the extracellular concentration of the competence-stimulating peptide (CSP), an exported peptide pheromone. Upon entering the competent state, pneumococci start transcribing a number of CSP-responsive genes, termed the early and late competence (com) genes. Some of the proteins encoded by these com genes are absolutely required for DNA uptake and transformation, but most of them are dispensable. This finding indicates that the majority of CSP-regulated proteins in S. pneumoniae is involved in processes unrelated to natural genetic transformation. Recently, however, it became clear that the biological role of a few of the dispensable proteins might be linked to the transformation process. Although these proteins are not needed for transformation per se, they constitute a killing mechanism that could be used by competent cells to acquire DNA from non-competent pneumococci. This mechanism, termed fratricide, has so far only been described for pneumococci. In this manuscript, we review evidence that suggests the conservation of fratricide as well as the independent evolution of its genetic control and of its effectors in several species of the genus Streptococcus, and discuss its possible biological significance in relation to natural transformation. [source] Antibody-dependent cell-mediated cytotoxicity to newly excysted juvenile Fasciola hepatica in vitro is mediated by reactive nitrogen intermediatesPARASITE IMMUNOLOGY, Issue 9 2001D. Piedrafita Passive intraperitoneal transfer of sera from Fasciola hepatica- infected sheep, cattle or rats can protect naive rats from F. hepatica infection, suggesting a parasite killing mechanism within the peritoneal cavity that is dependent on the presence of parasite-specific antibody. We investigated antibody-dependent cell-mediated cytotoxicity by resident peritoneal lavage cell populations, containing large numbers of monocytes/macrophages, as a potential host resistance mechanism by which juvenile flukes could be killed within the peritoneal cavity of naive rats. Comparative studies were conducted using cell populations containing large numbers of monocytes/macrophages from sheep. The results demonstrate that monocyte/macrophage-rich lavage cell populations from rat and sheep differ substantially in their ability to generate nitric oxide . Only resident rat peritoneal lavage cells were able to mediate antibody-dependent cell-mediated cytotoxicity against newly excysted juvenile liver fluke. The mechanism of cytotoxicity was dependent on, and directly proportional to, the production of nitric oxide and required attachment of effector cells to the newly excysted juvenile liver fluke tegument, which occurred following the addition of sera from F. hepatica -infected animals. This is the first report demonstrating a mechanism of cell-mediated cytotoxicity to newly excysted juvenile liver fluke. [source] Effect of preoperative prophylaxis with filgrastim in cancer neck dissectionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2000Wenisch Background Cancer surgery is known to lead to a deterioration in host defence mechanisms and an increase in susceptibility to infection after operation. Filgrastim enhances important antimicrobial functions of neutrophils including chemotaxis, phagocytosis and oxidative killing mechanisms. Methods The effects of additional (all patients received perioperative 3 , 25 mg kg,1 cefotiam and 1 , 20 mg kg,1 metronidazole) preoperative prophylaxis with filgrastim (5 ,g kg,1 12 h prior to surgery plus 5 ,g kg,1 0 h prior to surgery) on neutrophil phagocytosis and reactive oxygen radical production and postoperative infections in 24 patients undergoing cancer neck dissection were studied. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labelled Escherichia coli and Staphylococcus aureus by flow cytometry. Reactive oxygen generation after phagocytosis was estimated by determining the amount of dihydrorhodamine 123 converted to rhodamine 123, intracellularly. Results In the filgrastim-treated patients a higher neutrophil phagocytic capacity was seen intraoperatively, and 1,5 days postoperative, but not prior to surgery. Reactive oxygen radical production was significantly higher in filgrastim-treated patients prior to surgery, intraoperative and postoperative (1,5 days). 2/12 (17%) patients had postoperative infections in the filgrastim group and 9/12 (75%) patients had infections in the placebo group (P < 0.001). In particular, wound infections were recorded more often in the placebo group (1/12 vs. 6/12; P = 0.004). Conclusion We conclude that filgrastim enhances perioperative neutrophil function and could be useful in the prophylaxis of postoperative wound infections in patients undergoing cancer neck dissection. [source] The contribution of both oxygen and nitrogen intermediates to the intracellular killing mechanisms of C1q-opsonized Listeria monocytogenes by the macrophage-like IC-21 cell lineIMMUNOLOGY, Issue 1 2000C. Álvarez-Domínguez Summary Listeria monocytogenes is a facultative intracellular pathogen which is internalized by host mammalian cells upon binding to their surface. Further listerial growth occurs in the cytosol after escape from the phagosomal,endosomal compartment. We have previously reported that C1q is able to potentiate L. monocytogenes phagocytosis upon bacterial opsonization by ingestion through C1q-binding structures. In this report, we analysed the post-phagocytic events upon internalization of C1q-opsonized L. monocytogenes and found an induction of macrophage (M,)-like IC-21 cell bactericidal mechanisms displayed by the production of oxygen and nitrogen metabolites. Both types of molecules are effective in L. monocytogenes killing. Further analysis of the cellular responses promoted by interaction of C1q with its surface binding structures, leads us to consider C1q as a collaborative molecule involved in M, activation. Upon interaction with surface binding structures, C1q was able to trigger and/or amplify the production of reactive oxygen and nitrogen intermediates induced by stimuli such as interferon-, and L. monocytogenes phagocytosis. [source] Altered conjugate formation and altered apoptosis of multidrug-resistant human leukemia cell line affects susceptibility to killing by activated natural killer (NK) cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Robin S. Treichel Abstract Most leukemias that exhibit P-glycoprotein (P-gp)-associated multidrug resistance (MDR) exhibit reduced susceptibility to immune cytotoxicity mediated by natural killer (NK) cells. To explore this phenomenon we investigated N6/ADR, a doxorubicin-selected, P-gp-positive variant of the human acute lymphoblastic leukemia (ALL) cell line NALM6. Each stage of the NK cytolytic pathway, (binding, activation and killing) was evaluated to identify the alterations responsible for the reduced cytotoxicity of the variant relative to its drug-sensitive parental line. The major cause of the decreased susceptibility to NK cytolysis was found to be reduced conjugate formation by the MDR variant. Activation of NK effectors by parental and MDR cells with concomitant release of tumor necrosis factor-alpha (TNF-,) correlated with conjugate formation. N6/ADR was also more resistant than NALM6 to antibody-dependent cellular cytotoxicity and to cytotoxic factors released from NK cells as measured both by 51Cr-release and by DNA fragmentation. This is the first report of a P-gp-positive leukemic line that exhibits reduced conjugate formation as well as increased resistance to NK-mediated killing mechanisms. Our results suggest caution in the use of NK-based immunotherapy as an alternative treatment for multidrug-resistant leukemias. © 2003 Wiley-Liss, Inc. [source] Targeted immunotherapy of cancer: development of antibody-induced cellular immunityJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2003Yingjuan Lu ABSTRACT Although immunotherapy of cancer encompasses a large variety of distinct protocols, virtually all therapeutic strategies require the enabling/training of the immune system to distinguish tumour tissue from healthy tissue. In the case of antibody-based therapies, specificity obviously arises from the selectivity of the antibodies for tumour antigens, and tumour cell death derives from either direct cytotoxicity of the antibody or antibody-dependent cellular cytotoxicity. However, even when both of the above killing mechanisms are simultaneously active, we suggest that antibody-based immunotherapies may fall far short of their full potential. In this editorial, we first summarize the mechanisms by which current antibody-based therapies mediate cancer cell removal, and then propose two strategies by which this class of immunotherapies might be further improved. These suggested improvements involve the decoration of tumour cell surfaces with foreign haptens against which an endogenous humoral immune response can be mounted and the recruitment of the cellular arm of the immune system in an antibody-dependent process. [source] The flavonoid tangeretin activates the unfolded protein response and synergizes with imatinib in the erythroleukemia cell line K562MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 6 2010Sofie Lust Abstract We explored the mechanism of cell death of the polymethoxyflavone tangeretin (TAN) in K562 breakpoint cluster region-abelson murine leukemia (Bcr-Abl+) cells. Flow cytometric analysis showed that TAN arrested the cells in the G2/M phase and stimulated an accumulation of the cells in the sub-G0 phase. TAN-induced cell death was evidenced by poly(ADP)-ribose polymerase cleavage, DNA laddering fragmentation, activation of the caspase cascade and downregulation of the antiapoptotic proteins Mcl-1 and Bcl-xL. Pretreatment with the pancaspase inhibitor Z-VAD-FMK_blocked caspase activation and cell cycle arrest but did not inhibit apoptosis which suggest that other cell killing mechanisms like endoplasmic reticulum (ER)-associated cell death pathways could be involved. We demonstrated that TAN-induced apoptosis was preceded by a rapid activation of the proapoptotic arm of the unfolded protein response, namely PKR-like ER kinase. This was accompanied by enhanced levels of glucose-regulated protein of 78,kDa and of spliced X-box binding protein 1. Furthermore, TAN sensitized K562 cells to the cell killing effects of imatinib via an apoptotic mechanism. In conclusion, our results suggest that TAN is able to induce apoptosis in Bcr-Abl+ cells via cell cycle arrest and the induction of the unfolded protein response, and has synergistic cytotoxicity with imatinib. [source] | |||||||||||||