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1.
N.A. Maioli A.C. Zarpelon S.S. Mizokami C. Calixto-Campos C.F.S. Guazelli M.S.N. Hohmann F.A. Pinho-Ribeiro T.T. Carvalho M.F. Manchope C.R. Ferraz R. Casagrande W.A. Verri Jr 《Brazilian journal of medical and biological research》2015,48(4):321-331
It is currently accepted that superoxide anion (O2
•−) is an important mediator in pain and inflammation. The role of
superoxide anion in pain and inflammation has been mainly determined indirectly by
modulating its production and inactivation. Direct evidence using potassium
superoxide (KO2), a superoxide anion donor, demonstrated that it induced
thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be
determined whether KO2 is capable of inducing other inflammatory and
nociceptive responses attributed to superoxide anion. Therefore, in the present
study, we investigated the nociceptive and inflammatory effects of KO2.
The KO2-induced inflammatory responses evaluated in mice were: mechanical
hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot
plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt
pain-like behaviors (flinches, time spent licking and writhing score), leukocyte
recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative
PCR). Administration of KO2 induced mechanical hyperalgesia, thermal
hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching,
and paw licking in a dose-dependent manner. KO2 also induced
time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive,
inflammatory, and oxidative stress components of KO2-induced responses
were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid),
and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In
conclusion, the well-established superoxide anion donor KO2 is a valuable
tool for studying the mechanisms and pharmacological susceptibilities of superoxide
anion-triggered nociceptive and inflammatory responses ranging from mechanical and
thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte
recruitment. 相似文献
2.
L-selectin: Adhesion, signalling and its importance in pathologic posttraumatic endotoxemia and non-septic inflammation 总被引:1,自引:0,他引:1
Tanja Barkhausen Christian Krettek Martijn van Griensven 《Experimental and toxicologic pathology》2005,57(1):956-52
The leucocyte expressed surface-bound L-selectin belongs to the selectin family of adhesion molecules. It exhibits adhesive as well as signalling functions. Mainly, it is of importance in lymphocyte homing and in the extravasation of leucocytes into the surrounding tissue during inflammation. Acting in the initial step of the cell adhesion cascade, L-selectin is responsible for the rolling of leucocytes on endothelial layers. Therefore, L-selectin is thought to be an adequate target for pharmacological interventions. Beneath the discussion of the molecules' general features like molecule structure and its regulation, the review focuses firstly on L-selectin in the context of posttraumatic inflammatory disorders, and secondly on the importance of L-selectin specific signalling events. 相似文献
3.
Several age-related alterations occur at the cellular level in the immune system leading to a decrease in the immune response. The present study was designed to determine the effect of L-carnitine on impaired neutrophil functions of aged rats. For this reason, superoxide anion radical production, chemotaxis and phagocytic activity were studied in the neutrophils obtained from the peripheral blood of young and old rats. We orally gavaged L-carnitine (50 mg/kg b.w. per day) or control vehicle into young (2 months) and aged (24 months) rats for 30 consecutive days. The neutrophils of aged rats exhibited an increase in superoxide anion production and decline in phagocytosis and chemotaxis when compared with that in young rat neutrophils. Superoxide anion production in aged rats was significantly decreased by L-carnitine treatment which was accompanied with a significant enhancement of chemotactic and phagocytic activity being restored to control levels. These findings demonstrated that L-carnitine is capable of restoring the age-related changes of neutrophil functions. 相似文献
4.
Fabienne Venet Jeremy Schilling Marie-Angélique Cazalis Julie Demaret Fanny Poujol Thibaut Girardot Christelle Rouget Alexandre Pachot Alain Lepape Arnaud Friggeri Thomas Rimmelé Guillaume Monneret Julien Textoris 《Human immunology》2017,78(5-6):441-450
Septic patients develop immune dysfunctions, the intensities and durations of which are associated with deleterious outcomes. LILRB2 (leukocyte immunoglobulin-like receptors subfamily B, member 2), an inhibitory member of the LILR family of receptors, is known for its immunoregulatory properties.In a microarray study, we identified LILRB2 as an upregulated gene in septic shock patients. On monocytes primed with LPS ex vivo, LILRB2 mRNA and protein expressions were dose-dependently downregulated and subsequently highly upregulated versus non-stimulated cells. This is concordant with clinical data, since both LILRB2 mRNA and protein expressions were significantly increased in septic shock patients at day 3. In a cohort of more than 700 patients, only after septic shock were LILRB2 mRNA levels increased compared with non-infected or less severely infected patients. This was preceded by a phase of downregulated mRNA expression during the first hours after septic shock. Interestingly, the intensity of this decrease was associated with increased risk of death after septic shock.LILRB2 protein and mRNA expressions are deregulated on monocytes after septic shock and this can be reproduced ex vivo after LPS challenge. Considering LILRB2 inhibitory properties, we can hypothesize that LILRB2 may participate in the altered immune response after septic shock. 相似文献
5.
Nitsche JF Jiang SW Brost BC 《American journal of reproductive immunology (New York, N.Y. : 1989)》2011,66(3):242-248
Citation Nitsche JF, Jiang S‐W, Brost BC. Maternal neutrophil Toll‐like receptor mRNA expression is down‐regulated in preeclampsia. Am J Reprod Immunol 2011; 66: 242–248 Problem There are many immunological changes in preeclampsia. For example, TLR‐4 expression is increased in the placenta during preeclampsia. However, data on TLR expression in other tissues during preeclampsia are lacking. This study aimed to determine whether TLR mRNA expression in maternal neutrophils is altered in preeclampsia. Method of Study A case–control study using standard quantitative real‐time PCR techniques was performed to assess TLR‐2 and TLR‐4 mRNA expression in 12 patients with mild preeclampsia and 18 normal pregnant controls at similar gestational ages. Results Compared to normal pregnant controls, there was a significant decrease in TLR‐2 and TLR‐4 expression in women with mild preeclampsia. Conclusion TLR‐2 and TLR‐4 expression in maternal neutrophils is decreased in preeclampsia. Given the many immunological changes in preeclampsia, this may represent an adaptation to the increased inflammatory signals present in preeclampsia. Further study is needed to clarify the role of the TLR in preeclampsia. 相似文献
6.
7.
目的:探讨芒柄花黄素体外对氧自由基的抑制和清除作用。方法:采用分光光度法检测芒柄花黄素对超氧阴离子自由基(O2-)和羟自由基(.OH)的清除及抑制作用。结果:芒柄花黄素终浓度为10、20、40μg.ml-1时,在体外对O2-的清除率分别为42.19%,56.64%及65.43%,对O2-生成的抑制率分别为31.06%,44.72%及63.35%;而对.OH的清除率分别为34.98%,41.06%及61.60%。结论:芒柄花黄素对O2-具有明显的抑制及清除作用,其对.OH也有明显的清除作用。 相似文献
8.
Tortorella C Piazzolla G Spaccavento F Jirillo E Antonaci S 《Mechanisms of ageing and development》1999,110(3):283-205
Spontaneous as well as Fas-induced polymorphonuclear cell apoptosis is unchanged in the elderly. However, a weak responsiveness to antiapoptotic signals elicited by proinflammatory molecules has been reported in neutrophils isolated from aged humans. To gain insight into this field, here we have evaluated the role of oxidative metabolism and cyclic AMP (cAMP) signaling on age-related neutrophil apoptotic cell death. Results show that although superoxide dismutase (SOD), added exogenously to cell cultures, is able to prolong neutrophil survival in both young and aged individuals, high amounts of the enzyme are further effective in cell cultures of young donors only. Notably, the addition of catalase gives rise to a more striking, yet comparable, inhibition of neutrophil-programmed cell death in both groups of subjects. Furthermore, even low amounts of catalase are enough to restore a normal apoptotic outcome in SOD-treated cell cultures of old donors. Unlike the oxidative metabolism, cAMP signaling activation does not reveal any difference in the apoptotic response of neutrophils isolated from young and aged donors. Thus, supplementation of cell cultures with prostaglandin E2, dibutyryl cAMP or, to a lesser degree, forskolin results in a dose-dependent inhibition of DNA cleavage product appearance in both groups of subjects. The data outline that an impairment of neutrophil antioxidant shield, leading to an augmented cell oxidative load, is likely to occur as a feature of age. This may increase the apoptotic rate of stimulated cells, which may in turn account for the increased susceptibility of elderly individuals to life-threatening infections. 相似文献
9.
Neutrophil chemokine receptor expression can be altered by exposure to Toll-like receptor (TLR) agonists, a process that is thought to have the potential to localize neutrophils to sites of infection. In order to investigate this process in more detail, we examined the regulation of highly pure neutrophil CXCR1 and CXCR2 expression and function by selective agonists of TLR2 (Pam(3)CSK(4)) and TLR4 (lipopolysaccharide, LPS). CXCR1 and CXCR2 were down-regulated by TLR engagement. CXCR2 loss was more rapid and showed a dependence upon soluble helper molecules (LPS binding protein and CD14) that was not evident for CXCR1, suggesting differential coupling of LPS signalling to CXCR1 and CXCR2 loss. However, TLR engagement in highly pure neutrophils did not result in complete loss of chemokine receptors, and LPS-treated neutrophils remained able to mount a respiratory burst to CXCL8 and CXCL1, and were able to migrate towards CXCL8 in assays of under-agarose chemotaxis. Thus, although treatment of purified human neutrophils with TLR2 and TLR4 agonists modifies chemokine receptor expression, remaining receptors remain functionally competent. 相似文献
10.
吸烟对多形核白细胞的丙二醛含量及超氧化物歧化酶活性的影响 总被引:5,自引:0,他引:5
比较了非吸烟,吸烟,吸烟并慢阻肺者动脉血多形核白细胞的脂质过氧化产物—丙二醛(MDA)含量以及细胞和血清的抗氧化酶—超氧化物歧化酶(SOD)的活性。结果表明:吸烟和吸烟并慢阻肺者多形核白细胞的MDA以及SOD活性高于非吸烟者(P<0.01,P<0.05)。血清SOD则吸烟者低于不吸烟者(P<0.01)。MDA含量与SOD活性间的相关分析提示:吸烟者多形核白细胞的SOD处于相对不足,血清SOD绝对不足,练上所述:长期吸烟可使血中氧化和抗氧化失去平衡。 相似文献
11.
目的:比较脐血与成人外周血粒细胞Toll样受体(TLRs)的表达情况,为新生儿相关疾病的临床治疗积累实验资料。方法:取脐血和成人外周血,用密度梯度离心结合红细胞裂解法分离、收集粒细胞,流式细胞术鉴定粒细胞纯度,RT-qPCR检测TLRs 10个成员的mRNA表达水平,流式细胞术测定部分TLRs的蛋白荧光强度。结果:(1)流式细胞术检测结果:采用密度梯度离心结合红细胞裂解法分离收集的脐血粒细胞CD19-CD24+为(95.66±1.73)%,CD3+为(4.27±1.22)%,成人外周血粒细胞CD19-CD24+为(95.48±2.13)%,CD3+为(4.82±1.07)%。(2)RT-qPCR结果显示:脐血粒细胞和成人外周血粒细胞TLR1(0.141±0.091 vs 0.691±0.447)、TLR2(0.388±0.337 vs 0.901±0.508)、TLR4(0.093±0.071 vs 0.254±0.147)、TLR6(0.056±0.045 vs 0.202±0.034)、TLR7(0.001±0.001 vs 0.004±0.003)和TLR8(0.046±0.040 vs 0.211±0.146)的表达差异有统计学意义(P<0.01),TLR3、TLR5、TLR9和TLR10的表达差异无统计学意义(P>0.05);其中TLR3、TLR7和TLR9在脐血和成人外周血粒细胞的相对表达水平均较低。(3)流式分析显示脐血与成人外周血粒细胞TLR2平均蛋白荧光强度(21.40±3.09 vs 30.50±5.69)差异有统计学意义(P<0.05);而TLR4平均蛋白荧光强度差异无统计学意义(P>0.05)。结论:脐血粒细胞TLR1、TLR2、TLR4和TLR6 mRNA及TLR2蛋白表达低于成人外周血粒细胞,提示新生儿粒细胞识别细菌性病原微生物感染的能力可能存在缺陷或尚未完全成熟。这是否与新生儿急性细菌性毒血症发病及病死率较高有直接联系,有待进一步研究。 相似文献
12.
A rapid method for the simultaneous measurement of neutrophil superoxide generation and β-glucuronidase release is described. Assay of β-glucuronidase using a fluorescent substrate is shown to be valid in the presence of reduced or unreduced ferricytochrome C, a prerequisite for the simultaneous assessment of this enzyme activity and O2− generation. 相似文献
13.
The effect of maximal exercise on the activity of neutrophil granulocytes in highly trained athletes in a moderate training period 总被引:1,自引:0,他引:1
Summary Leucocyte cell counts and the phagocytic and chemotactic activities of neutrophil granulocytes were investigated in highly endurance-trained long-distance runners (n = 10) and triathletes (n = 10) during a moderate training period and compared with untrained subjects (n= 0) before and up to 24 h after a graded exercise to exhaustion on a treadmill. After exercise a leucocytosis was noted with a significant increase in lymphocyte (P0.01) and neutrophil (P0.01) counts in all groups. In neutrophils the number of ingested inert latex beads was significantly increased (P 0.01) from 0.21 (SD 0.09) to 0.45 (SD 0.22) in controls, from 0.20 (SD 0.12) to 0.56 (SD 0.16) in long-distance runners and from 0.25 (SD 0.08) to 1.03 (SD 0.42) particles per cell in triathletes 24 h after exercise, compared with resting values. The capability of neutrophils to produce microbicidal reactive oxygen species fell (P:_ 0.05) immediately after exercise in all subjects and then increased by 36 (SD 8) %, 31 (SD 6) % and 19 (SD 9) % in controls, runners and triathletes respectively up to 24 h after exercise (P 0.05) compared with pre-start values. With respect to the absolute number of neutrophils, ingestion capacity, production of superoxide anions and chemotactic activity, no significant differences were found between athletes and control subjects at rest and after exercise. These data indicate, on the one hand, no impairment of the granulocyte system during a moderate training period in long-distance runners and triathletes but, on the other, that the prolonged activation of the phagocytosis reaction after exercise might impair the granulocyte system in periods of intensive training with high training frequency. 相似文献
14.
J Gomez-Cambronero J L Mege T F Molski P H Naccache E L Becker R I Sha'afi 《International archives of allergy and applied immunology》1989,89(4):362-368
The protease inhibitor, phenylmethylsulfonyl fluoride inhibits granule enzyme release and, above 1 mM, superoxide production from rabbit peritoneal neutrophils induced by the chemotactic peptide, fMet-Leu-Phe. At concentrations below 1 mM, it enhances superoxide production. Superoxide generation stimulated by phorbol 12-myristate-13-acetate is increased by phenylmethylsulfonyl fluoride at all concentrations studied. Phenylmethylsulfonyl fluoride has no effect on the rise in intracellular calcium or the depolarization induced by fMet-Leu-Phe but does decrease the extent of repolarization and abolishes hyperpolarization. It depresses actin polymerization and abolishes cytoplasmic alkalinization caused by fMet-Leu-Phe. The increased phosphorylation induced by phorbol 12-myristate-13-acetate in four of the five proteins studied was not affected by phenylmethylsulfonyl fluoride, but the increased phosphorylation of the fifth, a 21-kD protein was enhanced. We conclude that phenylmethylsulfonyl fluoride acts on inhibitory and enhancing processes or steps induced by fMet-Leu-Phe which are subsequent to or independent of calcium mobilization and protein kinase C activity. 相似文献
15.
C. Chenevier-Gobeaux H. Lemarechal D. Bonnefont-Rousselot S. Poiraudeau O. G. Ekindjian D. Borderie 《Inflammation research》2006,55(11):483-490
Objectives to evaluate the rheumatoid synovial cell capacity to produce superoxide anion in response to interleukin-1β (IL-1β) and tumour
necrosis factor-α (TNF-α), and to study the NADPH oxidase involvement in this production.
Material and Methods Synovial cells obtained from 7 rheumatoid arthritis (RA), 5 osteoarthritic (OA) patients, and dermal fibroblasts, were stimulated
(i) with IL-1β and TNF-α, or (ii) with specific oxidase activators and inhibitors, before studying superoxide production;
we also studied NADPH oxidase mRNAs and protein expression, and p47-phox phosphorylation.
Results Constitutive superoxide production by RA cells was increased in comparison to OA cells and dermal fibroblasts, and was stimulated
by PMA and ionomycin. This production was increased after cytokine treatment of RA synovial cells. Cytokine-induced superoxide
production by RA cells was inhibited by iodonium diphenyl or apocynin, suggesting the involvement of NADPH oxidase. RT-PCR
and western blot analysis revealed the presence of p47-phox, gp91-phox and Nox4 in RA and OA cells, and in dermal fibroblasts. P47-phox phosphorylation was enhanced after cytokine-treatment in RA and OA cells, suggesting a PKC-mediated up-regulation of NADPH
oxidase.
Conclusions NADPH oxidase is involved in the superoxide release by RA synovial cells, constitutively and after cytokine up-regulation.
These cells express two different homologues (gp91-phox and Nox4).
Received 2 August 2005; returned for revision 12 January 2006; returned for final revision 22 May 2006; accepted by J. Di
Battista 9 June 2006 相似文献
16.
Dietary copper deficiency promotes neutrophil accumulation in rat lungs. We have now investigated the potential mechanisms of this effect. Male weanling rats were fed a Cu-adequate (6.0 mg diet) or Cu-deficient diet (0.30 mg) for 4 wks. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was measured in vivo and in vitro using a radiolabeled monoclonal antibody to rat ICAM-1. Tissue neutrophil accumulation was measured by myeloperoxidase (MPO) content and neutrophil transendothelial migration was assessed in vitro. Dietary copper deficiency had no effects on the expression of ICAM-1 in lung, liver, heart, kidney, or cremaster. However, MPO content was significantly greater in the lungs of copper-deficient rats. Endotoxin-induced ICAM-1 expression was greater in the lungs and hearts of copper-deficient rats. Similarly, cultured rat endothelial cells that were Cu-chelated expressed more ICAM-1 after endotoxin. This correlated with the significant increase in MPO in lungs of copper-deficient rats treated with endotoxin. The results suggest a tissue-specific difference in ICAM-1 expression and neutrophil accumulation during inflammation in copper-deficient rats. The findings suggest that lung inflammatory mechanisms are particularly sensitive to copper deficiency. 相似文献
17.
Stimulus-specific effects of pentoxifylline on neutrophil CR3 expression, degranulation, and superoxide production 总被引:3,自引:0,他引:3
M S Currie K M Rao J Padmanabhan A Jones J Crawford H J Cohen 《Journal of leukocyte biology》1990,47(3):244-250
The effects of pentoxifylline (Trental) on human neutrophil CR3 up-modulation, degranulation, and superoxide production were studied. We used the chemotactic peptide fMLP and the phorbol ester PMA as soluble stimuli, and beta-glucan particles as a CR3-specific solid phase stimulus of neutrophil superoxide production. Since neutrophils have adenosine A2 receptors, we compared effects of pentoxifylline to effects of adenosine, and we also looked at the effect of cytochalasin B, which breaks up actin filaments. Pentoxifylline inhibited both CR3 up-modulation and degranulation of myeloperoxidase and lysozyme. Pentoxifylline is a more potent inhibitor of fMLP- compared to PMA-induced degranulation, and is especially potent against superoxide production. While pentoxifylline is less potent than adenosine in its inhibition of fMLP-induced superoxide production, it is more potent in its inhibition of PMA- and beta-glucan particle-stimulated superoxide production. Cytochalasin B, which enhances degranulation and fMLP-stimulated superoxide production, was found to inhibit beta-glucan particle-stimulated superoxide production. These findings are consistent with the hypothesis that pentoxifylline can affect both the cytoskeletal architecture of unstimulated neutrophils and the activation and responses of neutrophils which involve actin polymerization and receptor-cytoskeletal interactions. 相似文献
18.
Thomas Felzmann Stephen Gadd Otto Majdic Dieter Maurer Peter Petera Josef Smolen Walter Knapp 《Journal of clinical immunology》1991,11(4):205-212
In this study we report the expression pattern of 13 different function-associated surface molecules on synovial fluid and peripheral blood granulocytes from rheumatoid and reactive arthritis patients. We found increased expression of the complement receptors 1 (CD35) and 3 (CD11b) and of the activation-associated antigens CD67, CD24, and M5 on synovial fluid granulocytes from rheumatoid and/or reactive arthritis patients compared to autologous peripheral blood granulocytes. In addition, synovial fluid granulocytes expressed IgG Fc receptor 1 (CD64) and complement receptor 4 (CD11c), neither of which can be found on peripheral blood granulocytes. Peripheral blood granulocytes from rheumatoid and reactive arthritis patients expressed higher levels of leucocyte function-associated antigen 1 (CD11a) and of the membrane proteins CD31, CD24, M5, and M6 compared to peripheral blood granulocytes from healthy controls and patients with degenerative joint disease. No significant differences in the expression of any of the molecules studied could be observed between cells from rheumatoid and cells from reactive arthritis patients, suggesting a similar activation process for granulocytes in these two diseases. 相似文献
19.
目的:观察肾病综合征(NS)患儿周围血中性粒细胞(PMN)凋亡的变化,并检测周围血中细胞因子IL-8、IL-6、TNF-α、NO和粘附分子P-选择素(P-sel)、细胞间粘附分子-1(ICAM-1)的水平,探讨细胞因子和粘附分子对PMN凋亡的影响。 方法:采用流式细胞术检测28例NS病人周围血PMN凋亡,ELISA法检测细胞因子和粘附分子水平。 结果:活动期NS患者PMN凋亡率明显低于健康人对照组和缓解期NS患者,缓解期NS患者PMN凋亡率与对照组无明显差别,不同病情活动期NS患者之间PMN凋亡有显著差异,活动期NS患者周围血中IL-8、IL-6、TNF-α、NO、P-sel 、ICAM-1水平均高于对照组和缓解组,且与PMN凋亡呈负相关,与病情呈正相关。缓解组患者IL-8 、IL-6、TNF-α、NO、P-sel和ICAM-1水平与对照组无显著差异。 结论: NS患者PMN凋亡延迟,且与病情及疗效密切相关。炎性细胞因子产生过多、免疫细胞粘附分子表达上调可能是导致PMN凋亡延迟的重要机制,适度调控PMN凋亡有可能会改善NS预后。 相似文献
20.
Eicosapentaenoic acid modulates neutrophil leukotriene B4 receptor expression in cystic fibrosis. 总被引:1,自引:0,他引:1 下载免费PDF全文
In patients with cystic fibrosis (CF), high intrapulmonary concentrations of the neutrophil chemotaxin leukotriene B4 (LTB4) are associated with specific reduction of LTB4-induced chemotaxis of circulating neutrophils. The chemotactic abnormality is partially corrected by dietary supplementation with eicosapentaenoic acid (EPA). LTB4-induced neutrophil chemotaxis is mediated by specific, high-affinity, cell surface LTB4 receptors. The hypotheses that neutrophil LTB4 receptors are down-regulated in CF, and that EPA normalizes receptor expression, were tested by measuring the number (Rmax) and affinity (Kd) of LTB4 receptors on neutrophils from eight CF patients before and after EPA (6 weeks of 2.7 g/day), and from nine normal individuals. High-affinity receptor Rmax was depressed in CF patients (0.6 +/- 0.2 x 10(4)/cell (mean +/- s.d.) versus 1.8 +/- 0.7 x 10(4)/cell in normals), but corrected to normal (2.0 +/- 1.9 x 10(4)/cell) after EPA. High-affinity receptor Kd was depressed in CF patients (0.4 +/- 0.3 nM versus 1.4 +/- 0.5 nM in normals), and also corrected to normal with EPA (1.4 +/- 1.2 nM). Low-affinity receptors were depressed, but did not change significantly with EPA. These results indicate that neutrophil responses in chronic inflammatory lung disease can be influenced directly by LTB4 receptor modulation, and that this effect of EPA predominates over alterations in neutrophil signal transduction in situations of chronic exposure to LTB4. 相似文献