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1.
The capacity of non-infected rat total, eosinophil-enriched and eosinophil-depleted fractions of peritoneal exudate and bone marrow cells to adhere to and killTrichinella spiralis newborn larvae with immune rat serum has been studied in vitro. The eosinophil-depleted peritoneal exudate cell fraction contained mainly mononuclear cells, whereas the corresponding bone marrow cell fraction consisted of a considerable number of neutrophils. All cell types either originating from the peritoneal cavity or the bone marrow, showed adherence and killing properties to the Trichinella newborn larvae. It was concluded that mononuclear cell and neutrophils are capable of and more effective than eosinophils in stage-specific killing of Trichinella in vitro.  相似文献   

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Y Shimizu  M Kurosawa 《Arerugī》1991,40(12):1521-1524
Peripheral blood eosinophils from the patients with atopic dermatitis were isolated on a Percoll gradient and incubated with H3(32)PO4. After stopping the reaction, SDS/PAG electrophoresis was performed and autoradiographs were prepared to determine the incorporation of 32P into proteins. Eosinophils developed at least 14 protein bands below 66.2 K by SDS/PAG electrophoresis and the differences of the staining patterns between hypodense and normodense eosinophils were observed. In the autoradiographs 5 distinct radioactive bands were observed below 31 K. 32P incorporation into the bands of hypodense eosinophils were stronger than that of normodense eosinophils, suggesting possible involvement of protein phosphorylation in the activation process of eosinophils.  相似文献   

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In this paper, we demonstrate that when a peripheral object is foveated by a sequence of multiple saccades, the initial saccade in the sequence is initiated markedly faster than a single accurate saccade to the same object. We suggest that multiple saccades represent a more automatic form of oculomotor planning that may be the result of a reduced influence from the cerebral cortex. To test this, we compared single and multiple saccade characteristics across development. We find that in contrast to the reduction in the latency of single saccades that is observed across development, the latency of initial saccades in multiple saccade sequences is remarkably stable across all age groups. Moreover, the longer the latency of this initial saccade, the more accurate it is, suggesting that there is a relation between the degree of procrastination and the accuracy of the response. Finally, the frequency with which multiple saccades occurred within each age group was positively correlated with the tendency to generate erroneous saccades during a fixation control task. Taken together, the present data suggest that multiple saccades are generated in a more automatic manner than single saccades.  相似文献   

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The "knockout-rate" prediction holds that essential genes should be more evolutionarily conserved than are nonessential genes. This is because negative (purifying) selection acting on essential genes is expected to be more stringent than that for nonessential genes, which are more functionally dispensable and/or redundant. However, a recent survey of evolutionary distances between Saccharomyces cerevisiae and Caenorhabditis elegans proteins did not reveal any difference between the rates of evolution for essential and nonessential genes. An analysis of mouse and rat orthologous genes also found that essential and nonessential genes evolved at similar rates when genes thought to evolve under directional selection were excluded from the analysis. In the present study, we combine genomic sequence data with experimental knockout data to compare the rates of evolution and the levels of selection for essential versus nonessential bacterial genes. In contrast to the results obtained for eukaryotic genes, essential bacterial genes appear to be more conserved than are nonessential genes over both relatively short (microevolutionary) and longer (macroevolutionary) time scales.  相似文献   

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Fifteen unencapsulated B. fragilis strains isolated from human infections were examined for their capability to hemagglutinate erythrocytes of different species. Seven strains were found to hemagglutinate guinea pig and human (A,B,O) erythrocytes. This hemagglutination was resistant to treatment with D-mannose and several other sugars. Hemagglutinating strains were also capable of adhering to human epithelial cells and cultured human cell line (Intestine 407) and were 6- to 20-fold more adhesive than non-hemagglutinating strains. Pilus-like structures were found in negative-stained preparations on the hemagglutinating (and adhesive) strains but not on the others. Hemagglutinating and adhesive bacteria were 3- to 7-fold more sensitive to phagocytosis and 5- to 10-fold more sensitive to killing by human neutrophils than non-hemagglutinating ones.  相似文献   

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The role of eosinophils and neutrophils in inflammation   总被引:9,自引:0,他引:9  
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Glioblastoma multiforme (GBM) is the most dramatic primary brain cancer with a very poor prognosis because of inevitable disease recurrence. The median overall survival is less than 1 year after diagnosis. Cancer stem cells have recently been disclosed in GBM. GBM stem‐like cells (GSCs) exhibit resistance to radio/chemotherapeutic treatments and are therefore considered to play an important role in disease recurrence. GSCs are thus appealing targets for new treatments for GBM patients. In this study, we show that GBM cells with stem cell characteristics are resistant to lysis mediated by resting natural killer (NK) cells because of the expression of MHC class I molecules. However, GSCs are killed by lectin‐activated NK cells. Furthermore, in experiments using the therapeutic antibody CetuximAb, we show that GSCs are sensitive to antibody‐mediated cytotoxicity. We confirm the sensitivity of GSC to cytotoxicity carried out by IL2‐activated NK cells and tumor‐specific T cells. More importantly, we show that GSCs are more sensitive to NK and T cell‐mediated lysis relatively to their corresponding serum‐cultured GBM cells obtained from the same initial tumor specimen. Altogether, these results demonstrate the sensitivity of GSC to immune cell cytotoxicity and, therefore, strongly suggest that GSCs are suitable target cells for immunotherapy of GBM patients.  相似文献   

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In the absence of antimicrobial therapy, bacteria such as Bacteriodes fragilis, Escherichia coli and Proteus mirabilis may persist within an intra-abdominal abscess in the presence of large numbers of neutrophils which, under optimal conditions in vitro, can readily phagocytose and kill the same bacterial strains. Neutrophils taken from abscesses induced by gram-negative bacteria such as those above contain viable organisms. On incubation in vitro in the presence of serum, these neutrophils kill the bacteria phagocytosed in the abscess poorly, if at all, yet can readily kill organisms added in vitro. To determine possible mechanisms that might explain this, we examined the bactericidal activity in vitro of neutrophils from a range of abscesses induced by one or two species of bacteria plus an abscess-potentiating agent, bran. The organisms studied were B. fragilis, E. coli, P. mirabilis and Staphylococcus aureus. The killing in vitro of E. coli and P. mirabilis, engulfed within an abscess, was significantly less than that of the same organisms when they were added to the in-vitro assay. In contrast, the killing of S. aureus was similar, whether engulfed in vivo or in vitro. However, S. aureus was less susceptible to phagocytosis and killing in vitro than P. mirabilis or E. coli, and the killing of S. aureus during in-vitro incubation of neutrophils that had engulfed the organism with in the abscess was similar to that of the gram-negative bacteria engulfed within the abscess.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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Nearly a hundred years of scientific research has revealed a notable preference of cancer cells to utilize aerobic glycolysis rather than mitochondrial oxidative phosphorylation for glucose-dependent ATP production, which is thought to be the root of tumor formation and growth. Glycolysis is a complex biochemical process that is mediated by multiple glycolytic genes. Besides regulating glucose metabolism, these genes are also suggested to possess various other functions related to cancer, including roles in cancer development and promotion, inhibition of apoptosis, cell cycle progression, and tumor metastasis. This article highlights the biological functions of glycolytic genes beyond their role in regulation of glycolysis and discusses their clinical implications, especially in regard to the use of glycolytic genes as biomarkers for early detection of cancer or as targets for novel anticancer treatments.  相似文献   

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BACKGROUND: Recent studies suggest that serine proteases are involved in various biological responses through activation of protease-activated receptors (PARs). However, the functions of other proteases, such as cysteine proteases, are poorly understood and need elucidation. OBJECTIVE: We examined the effects of an authentic cysteine protease, papain, and a protease derived from the mite allergen, Der f 1, on functions of human eosinophils. METHODS: Purified eosinophils were incubated with papain or Der f 1. Eosinophil activation was monitored by superoxide anion generation and by degranulation. Intracellular signaling pathways were investigated through use of pharmacologic approaches. RESULTS: We found that papain potently induces human eosinophils to degranulate and to produce superoxide anion. A cysteine protease inhibitor, E-64, abolished the stimulatory effects of papain, which suggests that the protease activity of papain is necessary to trigger eosinophil responses. The eosinophil's response to papain was enhanced by IL-5 and mediated by activation of the phosphatidylinositol 3-kinase/Akt pathway. Interestingly, whereas a serine protease, trypsin, activated eosinophils through PAR2, the effects of papain were not inhibited by an antibody to PAR2, which suggests another novel mechanism for the eosinophils' response to cysteine proteases. It is likely that these observations are clinically important, because eosinophils were activated by a natural cysteine protease allergen, Der f 1, and released granule proteins. CONCLUSION: Human eosinophils are probably equipped with machineries that recognize and respond to cysteine proteases, such as those found at allergic inflammation sites; the result is active release of proinflammatory mediators.  相似文献   

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Human eosinophils can mediate both beneficial and detrimental responses in parasitic and allergic diseases. Binding of aggregated immunoglobulin to Fc receptors on eosinophils mediates important defence processes, including generation of activated oxygen species resulting from NADPH oxidase activation, and eosinophil peroxidase release following degranulation. The abilities of a matched set of IgA, IgG and IgE antibodies to elicit such responses in blood-derived eosinophils were compared using a chemiluminescence assay. IgA and IgG, but not IgE, were found to trigger NADPH oxidase activation and degranulation in eosinophils. This non-responsiveness to IgE did not result from receptor blockade by endogenous IgE since no blood-derived IgE was detectable on freshly isolated eosinophils. Moreover, while cross-linking of FcalphaRI by specific mAbs triggered NADPH oxidase activation and degranulation in blood-derived eosinophils, equivalent cross-linking of FcvarepsilonRI or FcvarepsilonRII did not elicit such responses. Therefore IgA is more potent at eliciting activated oxygen species release and degranulation in eosinophils than IgE, suggesting that the importance of IgA in eosinophil activation in immune defence and allergy may have been underestimated.  相似文献   

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Peripheral blood eosinophils from patients with atopic dermatitis and normal healthy controls were isolated on a Percoll gradient and were incubated with [32P]orthophosphoric acid. After stopping the reaction, SDS/PAGE was performed and autoradiographs were prepared to determine the incorporation of 32P into proteins. Eosinophils developed at least 14 protein bands below 66.2 kDa by SDS/PAGE and the differences of the protein staining patterns between hypodense and normodense eosinophils were present. In the autoradiographs five distinct radioactive bands were observed below 31 kDa. 32P incorporation into the bands of hypodense eosinophils was stronger than that of normodense eosinophils, suggesting possible involvement of protein phosphorylation in the activation process of human eosinophils.  相似文献   

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BACKGROUND: Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by the presence of eosinophils and neutrophils. However, the mechanisms that mediate the influx of these cells are incompletely understood. Neutrophil products, including neutrophil elastase and antimicrobial peptides such as neutrophil defensins and LL-37, have been demonstrated to display chemotactic activity towards cells from both innate and adaptive immunity. However, chemotactic activity of LL-37 towards eosinophils has not been reported. Therefore, the aim of the present study was to investigate the chemotactic activity of LL-37 for eosinophils and to explore the mechanisms involved in LL-37-mediated attraction of neutrophils and eosinophils. METHODS: Neutrophils and eosinophils were obtained from venous blood of healthy donors. Chemotaxis was studied using a modified Boyden chamber technique. Involvement of formyl-peptide receptors (FPRs) was studied using the antagonistic peptide tBoc-MLP. Activation of the mitogen-activated protein kinase (MAPK) ERK1/2 was studied by Western blotting using antibodies directed against phosphorylated ERK1/2. RESULTS: Our results show that LL-37 chemoattracts both eosinophils and neutrophils. The FPR antagonistic peptide tBoc-MLP inhibited LL-37-induced chemotaxis. Whereas the FPR agonist fMLP activated ERK1/2 in neutrophils, LL-37 did not, indicating that fMLP and LL-37 deliver different signals through FPRs. CONCLUSIONS: LL-37 displays chemotactic activity for eosinophils and neutrophils, and this activity is mediated via an FPR. These results suggest that LL-37 may play a role in inflammatory lung diseases such as asthma and COPD.  相似文献   

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Type 1 T-cell responses against intracellular pathogens play a crucial role in mediating protection. We examined whether the induction of a strong type 1 T-cell response during a chronic bacterial infection influences responses to superantigens capable of inducing acute shock. Intravenous infection of mice with Mycobacterium bovis BCG appeared to induce a progressive anergy towards staphylococcal enterotoxin B (SEB) and towards antigen preparation of BCG (BCG-Ag) itself, based on diminished gamma interferon (IFN-gamma) production by SEB- and BCG-Ag-stimulated splenocytes from infected mice. In contrast to these in vitro results, injection of SEB into BCG-infected mice led to a dramatic increase in the serum IFN-gamma levels and the death of infected but not of control mice. In vitro hyporesponsiveness towards SEB and BCG-Ag occurred only with unfractionated splenocyte cultures, as purified T cells from infected mice produced higher levels of IFN-gamma. Hyporesponsiveness towards SEB and BCG-Ag in unfractionated splenocyte cultures was not due to suppressive antigen-presenting cells (APCs), as APCs from infected mice stimulated higher levels of IFN-gamma from purified T cells. The diminished IFN-gamma levels observed with bulk splenocytes appear to be due to changes in the T-cell-to-APC ratio that result in a decreased proportion of T cells, coupled to reduced proliferative responses and an increased susceptibility of effector T cells to activation-induced cell death in vitro. Our results indicate that the reported phenomena of T-cell anergy during mycobacterial infection may be an in vitro consequence of the development of a strong type 1 response in vivo.  相似文献   

19.
Participation of eosinophils in the toxic oil syndrome.   总被引:2,自引:0,他引:2       下载免费PDF全文
The participation of eosinophils in the Spanish toxic oil syndrome (TOS) was investigated. Eosinophil infiltration and degranulation in tissues from 52 patients with the TOS were examined by immunofluorescence staining for the eosinophil granule major basic protein (MBP). Serum MBP levels were determined in sera from 323 patients. Eosinophil infiltration and degranulation were found in several tissues, especially during the acute phase of the TOS, and serum MBP was significantly elevated during all phases of the disease, suggesting that eosinophils play a role in the pathogenesis of the TOS.  相似文献   

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The research field on e-cigarettes is characterized by severe methodological problems, severe conflicts of interest, relatively few and often small studies, inconsistencies and contradictions in results, and a lack of long-term follow-up. Therefore, no firm conclusions can be drawn on the harm of e-cigarettes, but they can hardly be called safe. Experimental studies indicate negative health effects and, amongst others, the major ingredient propylene glycol warrants concern. Growing evidence raises doubt about the efficacy of e-cigarettes as a smoking cessation aid. Unfortunately, it seems that many smokers use e-cigarettes with the intention to quit but switch to long-term use of e-cigarettes or dual use. Use is spreading rapidly to minors, ex-smokers, and never-smokers. It is questionable whether the potential health benefits obtained by some smokers outweigh the potential harm by use of non-smokers, of undermining of complete cessation, smokers’ dual use, and of eventual re-normalization of smoking. Even if e-cigarettes are significantly less harmful than conventional cigarettes, the product may have a very negative impact on public health if its use is spread to a large part of the population.  相似文献   

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