Suppressive effects of linoleic acid on neutrophil oxygen metabolism and phagocytosis

On the basis of recent reports that the proportion of linoleic acid (C18:2Cis 9,12), a free fatty acid, is markedly decreased in acne comedones and that tetracycline is effective against acne comedones by acting directly as an antioxidant on infiltrating neutrophils, we investigated the effect of linoleic acid on several inflammatory parameters of neutrophils, including neutrophil chemotaxis, phagocytosis, and generation of reactive oxygen species (ROS). Linoleic acid significantly decreased phagocytosis and the generation of O2-, H2O2, and OH.by neutrophils, whereas it did not significantly inhibit neutrophil chemotaxis or decrease the ROS levels generated in a cell-free, xanthine-xanthine oxidase system. The present study seems to suggest that decreased levels of linoleic acid in acne comedones contribute, in part, to the worsening of acne inflammation by the failure of low levels of linoleic acid to suppress neutrophil phagocytosis and ROS generation.     

Effect of palmitic acid on neutrophil functions in vitro

BACKGROUND: It has been shown that in acne comedones the proportion of linoleic acid is markedly decreased, while palmitic acid is significantly increased. We previously reported that the decreased proportion of linoleic acid, which markedly suppresses neutrophil reactive oxygen species (ROS) generation and phagocytosis, contribute to the worsening of acne inflammation. The aim of this study was to examine the effect of palmitic acid on neutrophil functions in vitro. METHODS: We investigated the effect of palmitic acid on inflammatory parameters such as neutrophil chemotaxis, phagocytosis, and ROS generation. Reactive oxygen species generation in a cell-free, xanthine-xanthine oxidase system was also assessed. The species examined were superoxide radical anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH.). RESULTS: Palmitic acid significantly decreased H2O2 generation both by neutrophils and in the xanthine-xanthine oxidase system, while neutrophil chemotaxis and phagocytosis as well as O2- and OH. generation by both systems were not markedly affected in the presence of palmitic acid. CONCLUSIONS: The present study suggests that palmitic acid may be involved in the pathogenesis of acne inflammation from a standpoint of oxidative tissue injury.     

Inhibitory effect of azelaic acid on neutrophil functions: a possible cause for its efficacy in treating pathogenetically unrelated diseases

Summary It has been shown that acne, hyperpigmentation and lentigo malignant are more or less related pathogenetically to reactive oxygen species (ROS). It has recently been reported that azelaic acid is effective in treating these conditions and that it possesses anti-enzymatic and anti-mitochondrial activity, including cytochrome-P₄₅₀ reductase and 5-reductase in microsomal preparations with nicotinamide adenine dinucleotide phosphate (NADPH). We therefore investigated the effects of azelaic acid on human neutrophil functions, such as chemotaxis, phagocytosis and ROS generation. ROS generation in a cell-free system was also assessed. The results revealed that neutrophil chemotaxis and phagocytosis as well as ROS generated in a xanthine — xanthine-oxidase system were not significantly changed in the presence of azelaic acid. However, azelaic acid markedly decreased O ₂ ^– and OH generated by neutrophils. It may be concluded that the reported clinical effectiveness of azelaic acid is partly due to its inhibitory action on neutrophil-generated ROS, leading to a reduction both in oxidative tissue injury at sites of inflammation and in melanin formation.     

Effects of subminimal inhibitory concentrations of minocycline on neutrophil chemotactic factor production in comedonal bacteria,neutrophil phagocytosis and oxygen metabolism

Summary Comedonal bacteria, Propionibacterium acnes, P. granulosum and coagulase-negative staphylococci (CNS) seem to play an important initiating role in the inflammatory process by producing neutrophil chemotactic factors. The attracted neutrophils, after phagocytosis, release inflammatory factors such as reactive oxygen species (ROS). We investigated the effects of minocycline at subminimal inhibitory concentrations (sub-MIC), i.e. one-tenth MIC, on the production of human neutrophil chemotactic factors in comedonal bacteria, and on several inflammatory parameters of neutrophils, including neutrophil phagocytosis and generation of ROS (O ₂ ^– , H₂O₂, O ). ROS generation in a cell-free, xanthinexanthine oxidase system was also assessed. Production of neutrophil chemotactic factors in all strains of P. acnes, P. granulosum and CNS were significantly suppressed by sub-MIC minocycline. Sub-MIC minocycline effectively reduced three kinds of neutrophil-generated ROS (O ₂ ^– , H₂O₂, O ). However, neutrophil phagocytosis and the ROS generated in a cell-free system were not markedly changed in the presence of sub-MIC minocycline. The results suggest that sub-MIC minocycline has an anti-inflammatory effect by inhibiting the production of neutrophil chemotactic factors in comedonal bacteria as well as ROS generated by neutrophils in the inflammatory process of acne.     

Anti-oxidant effects of gold compounds

The anti-oxidant efficacy, in vitro, of the gold compounds auranofin (AF) and gold sodium thiomalate (GST) was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leukocytes (PMNs) and a cell-free, xanthine-xanthine oxidase system. The oxygen species investigated were the superoxide radical anion (O2-), hydrogen peroxide (H2O2) and the hydroxyl radical (OH.). AF had an inhibitory effect on ROS production by PMNs. In particular, OH. generation was significantly suppressed in a dose-dependent fashion. AF did not inhibit ROS production in the cell-free system. GST produced only a small degree of inhibition at higher concentrations. These findings suggest that AF may play an important role in the inhibition of respiratory bursts and the generation of inflammatory reaction products. Since the products of the respiratory burst, especially potent oxidants such as OH. and H2O2, are thought to be important inflammatory mediators, it is postulated that the blockade of toxic ROS generation by AF affects rheumatoid as well as dermatological inflammation and tissue damage.     

Effect of doxycycline on the generation of reactive oxygen species: a possible mechanism of action of acne therapy with doxycycline.

On the basis of a recent report that minocycline is effective in the treatment of acne inflammation by acting directly as an antioxidant on infiltrating neutrophils, we investigated whether doxycycline might also be capable of reducing the generation of reactive oxygen species, using human neutrophils and a cell-free, xanthine-xanthine oxidase system. The species investigated are superoxide radical anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). Doxycycline significantly reduced the levels of O2-, H2O2 and OH. generated by both systems. Our results seem to suggest that the clinical effectiveness of doxycycline in the treatment of acne inflammation is due partly to its antioxidant effect on neutrophils.     

Factors secreted by untreated psoriatic monocytes enhance neutrophil functions

Monocytes stimulated with bacterial lipopolysaccharides (LPS) release mediators that induce increased responses of human granulocytes. Recently we showed that psoriatic monocytes can stimulate neutrophil chemotaxis, phagocytosis, and O2- production without addition of LPS and this effect is inhibited by cyclosporin A. We have now investigated the presence of cytokines in supernatants from cultures of psoriatic monocytes (resting monocytes). These cells were cultured for 24 h in endotoxin-free medium. Normal human neutrophils were then incubated for 1 h with the resulting supernatants (sMS, or conditioned media). The sMS from unstimulated psoriatic monocytes significantly enhanced neutrophil chemotaxis and superoxide anion production. The enhancing factors are protein in nature and require ongoing protein synthesis, demonstrated by the facts that the activity in conditioned medium is labile to heat denaturation at 100 degrees C for 10 min, is not produced by monocytes cultured in the presence of puromycin, and is proteinase sensitive. Additional evidence suggested that extremes of pH inhibit activity. None of the conditioned media treated in these ways activated neutrophils. The neutrophil function-enhancing factors derived from psoriatic monocytes are in part cytokines, including TNF and GM-CSF. The support for this conclusion is the higher level of TNF and GM-CSF in media conditioned by psoriatic monocytes than in media conditioned by normal human monocytes, the inhibition of TNF production and neutrophil stimulating activity by cyclosporin A, and the inhibition of neutrophil stimulating activity in conditioned media preincubated with anti-TNF and anti-GM-CSF antibodies. It is concluded that psoriatic monocytes spontaneously produce higher than normal levels of TNF alpha, GM-CSF, and, perhaps, other cytokines that might be responsible for the enhanced activity of psoriatic neutrophils.     

In vitro studies on microphage functions in chronic pyoderma vegetans

Summary The function of microphages has been studied in two patients with chronic pyoderma vegetans by in vitro determination of phagocytosis as well as chemotaxis. The results showed a striking decrease in the chemotactic activity of the neutrophil granulocytes, a reduced phagocytosis of Candida albicans and Staphylococcus aureus, and a weakness of the intracellular killing of these microorganisms. However, the NADH-dependent oxidase activity appeared to be intact. No defect was found in the specific cellular or humoral immune system in either patient.Supported by grant Dj2/2 of the Deutsche Forschungsgemeinschaft     

Neutrophil dysfunction and repeated infections: influence of levamisole and ascorbic acid

Neutrophil function was studied in several patients with recurrent infections, mainly of the skin. Twelve patients showed impairment of neutrophil functions, either chemotaxis or bacterial killing and phagocytosis. Levamisole was given in four cases: improvement of neutrophil function and long-lasting clinical remission occurred in three of them, whilst in the fourth the drug was not tolerated. Ascorbic acid was administered to three other patients, with satisfactory improvement of neutrophil function and long-lasting clinical remission.     

Age-dependent generation of reactive oxygen species in the skin of live hairless rats exposed to UVA light

Aging proceeds by highly complicated biochemical processes, in which the involvement of the reactive oxygen species (ROS) and free radicals has been implicated. Although the relationship between UV-induced photoaging and ROS generation has been proposed, it has been difficult to establish direct proof of the generation of ROS in the skin under UV exposure. Recently, we reported finding endogenously generated ROS in the skin of live mice after UVA light exposure by a method of in vivo chemiluminescent detection, in which superoxide anion radical (*O2-) and singlet oxygen species (1O2) are contributed. In light of the results, we tried to understand the age-dependent changes in ROS generation in the skin of hairless rats under UVA exposure. Chemiluminescent levels due to ROS in the untreated and UVA-exposed skin decreased age dependently, and the signal intensities in old rats were significantly lower than those in young rats. However, the ratios of chemiluminescent intensities in the UVA-exposed skin to those in the untreated skin were significantly enhanced in an age-dependent manner. These results suggest that the antioxidative ability against ROS generation in the skin, possessed by antioxidant enzymes and low molecular weight antioxidants, is lowered age dependently.     

芹黄素对过氧化氢所致黑素细胞凋亡的作用

目的采用过氧化氢(H2O2)诱导的黑素细胞体外氧化应激模型探讨芹黄素对黑素细胞的抗氧化保护作用。方法采用MTT法测定不同浓度芹黄素预处理前后H2O2对正常人表皮黑素细胞活力的影响,An-nexin-V/PI双染流式细胞术检测细胞的凋亡情况,DCFH-DA流式细胞术检测细胞活性氧(ROS)的含量。结果 250μmol/L的H2O2作用于黑素细胞24h,黑素细胞活力降低至(36.42±7.21)%,凋亡率增加至(48.82±12.55)%。0.6μmol/L,2.5μmol/L和10.0μmol/L芹黄素预处理1h后,H2O2所致细胞活力分别增加至(41.53±5.25)%,(45.33±6.28)%和(51.92±5.29)%,凋亡率减少至(42.25±7.69)%,(37.54±8.82)%和(32.25±58.28)%。250μmol/L的H2O2作用于黑素细胞2h后,黑素细胞ROS含量增加至空白对照组的(69.22±8.57)倍。10μmol/L芹黄素预处理1h后H2O2所致黑素细胞ROS含量为空白对照组的(54.48±5.03)倍,低于单用H2O2处理组。结论芹黄素可能通过减少ROS生成和抑制氧化应激对HO所致黑素细胞凋亡具有保护作用,其可能具有开发为治疗白癜风新药的前景。     

DJ-1降低细胞内ROS并抑制细胞凋亡保护黑素细胞抵抗H202诱导的氧化应激北大核心CSCD

目的探讨DJ-1蛋白在原代培养的人黑素细胞中的表达以及抵抗HO诱导的氧化应激作用。方法免疫荧光方法鉴定DJ-1在原代培养黑素细胞中的表达;使用不同浓度HO处理黑素细胞24 h,改良MTT法选取适宜HO浓度为后续实验条件;Western印迹检测HO处理组细胞内DJ-1表达变化;采用反向转染方法 ,实验分为空白对照组(不含siRNA片段)、阴性对照组(转染非特异性siRNA)和实验组(转染DJ-1特异性siRNA)。光学显微镜观察细胞贴壁后形态学差异;改良MTT法、荧光探针2’,7’-二氯荧光黄双乙酸盐(DCFH-DA)、膜联蛋白V-异硫氰酸荧光素/碘化丙啶(AnnexinV-FITC/PI)分别检测HO处理后细胞活力变化、细胞内活性氧(ROS)水平及凋亡比例。结果免疫荧光显示DJ-1在黑素细胞细胞核和胞质中均表达,以细胞核表达为主;细胞活力随HO浓度增高呈剂量依赖关系下降,与对照组比较,0.5 mmol/L HO处理24 h后,细胞活力开始下降(P<0.05)。做诱导氧化应激的实验条件;Western印迹结果显示,0.5 mmol/L HO处理细胞24 h后,DJ-1表达增高为HO未处理组的2.23倍(P<0.05)。干涉DJ-1表达后,实验组黑素细胞形态与空白对照组相比,树突减少缩短,胞质空泡化改变。使用0.5 mmol/L HO处理24 h后,siRNA-DJ-1组细胞活力为对照组的35%(P<0.05)。细胞内ROS的荧光密度值(FI)值(902±40)和凋亡比例(58%±6.1%)增高,与空白对照组细胞内ROS的FI值(529±32)和凋亡比例(30%±3.8%)相比,P值均<0.05。结论 DJ-1在黑素细胞中能够通过降低细胞内ROs水平和抑制细胞凋亡,从而抵抗HO所诱导的氧化应激。     

咖啡酸衍生物WSY6对黑素细胞氧化应激损伤的保护作用及机制研究

目的 探讨咖啡酸衍生物WSY6对过氧化氢（H2O2）诱导的黑素细胞氧化损伤的保护作用和潜在分子机制。方法 体外培养原代人表皮黑素细胞,分为对照组（不做任何处理）、H2O2组（1 mmol/L H2O2处理）和6.25、12.5、25 μmol/LWSY6组（分别用6.25、12.5、25 μmol/L WSY6预处理1 h后再用1 mmol/L H2O2处理1 h）。继续培养24 h后,用MTS法测定黑素细胞存活率,乳酸脱氢酶（LDH）试剂盒检测LDH释放量。部分黑素细胞分为抑制剂组（用p38抑制剂预处理1 h,再用1 mmol/L H2O2处理1 h）和H2O2组（直接用1 mmol/L H2O2处理1 h）,处理完成后继续培养24 h,用试剂盒检测LDH的释放量。部分黑素细胞用25 μmol/L WSY6预处理1、2、4 h后,再用H2O2处理1 h,流式细胞仪检测细胞内活性氧（ROS）水平;部分黑素细胞用6.25、12.5、25 μmol/L WSY6处理1 h后,再用H2O2处理1 h,Western印迹法检测细胞色素C（cyto?c）、半胱氨酸天冬氨酸蛋白酶3（caspase?3）、caspase?9和磷酸化丝裂原活化的蛋白激酶（p?p38 MAPK）、细胞外调节蛋白激酶（p?ERK）及c?Jun氨基末端激酶（p?JNK）的表达。结果 与对照组相比,H2O2组黑素细胞存活率明显降低（29.22% ± 1.31%,P < 0.05）,细胞内LDH释放量增加（47.19% ± 4.85%,P < 0.05）,ROS水平明显升高（18.37 ± 1.59,P < 0.05）,caspase?3和caspase?9的表达亦均升高。与H2O2组相比,6.25、12.5、25 μmol/L WSY6组细胞存活率明显增加（52.48% ± 1.17%、60.21% ± 0.25%、78.32% ± 1.73%,P < 0.05）,LDH释放量明显下降（21.99% ± 0.22%、15.38% ± 0.45%、13.18% ± 0.38%,均P < 0.05）,25 μmol/L WSY6处理1、2、4 h组细胞内ROS显著下降（7.59 ± 1.00、6.22 ± 0.52、5.15 ± 0.48,均P < 0.05）。同时p38抑制剂组黑素细胞LDH释放量较H2O2组显著下降（P < 0.05）。Western印迹法显示,WSY6预处理后,与H2O2组相比,caspase?3和caspase?9表达明显降低,p?p38表达下降,但p?ERK和p?JNK表达无明显变化;同时WSY6组p38 MAPK下游产物p?p53表达也下降,且WSY6浓度越高,下降越明显。结论 WSY6对H2O2诱导的黑素细胞氧化应激损伤有显著的保护作用,可能通过p38 MAPK途径发挥作用。     

维生素C溶液在H2O2诱导体外培养黑素细胞氧化损伤中的影响

目的：探讨维生素C对体外培养的人黑素细胞增殖活性的影响并评估维生素C对H2O2诱导的人黑素细胞氧化损伤的影响。方法通过CCK8法取最佳浓度的维生素C溶液和半数致死浓度的H2O2溶液应用于实验。将黑素细胞分为对照组、维生素C组、H2O2组、联合处理组4组,经过48 h处理后,分别用CCK8法和流式细胞仪检测4组细胞活率及凋亡率;将除维生素C组以外其他3组细胞,分别用生物化学法检测超氧化物歧化酶活力和丙二醛浓度,荧光染色法检测细胞内的活性氧。结果最佳浓度的维生素C溶液为1000μmol/L,半数致死浓度的H2O2溶液300μmol/L。对照组细胞活率、细胞凋亡率、超氧化物歧化酶活力、丙二醛浓度、活性氧荧光强度分别为（100±4.99）％、（6.90±0.87）％、（54.71±4.75）U/mgprot、（263.39±20.17）nmol/mgprot、342.16±27.36。H2O2溶液可以明显提高黑素细胞凋亡率[（16.47±1.07）％]、超氧化物歧化酶活性[（103.62±10.44）U/mgprot]、丙二醛[（493.70±31.36）nmol/mgprot]和细胞内活性氧（782.48±36.25）水平,降低细胞活率[（39.07±2.94）％],而维生素C溶液可以显著降低H2O2溶液诱导的凋亡[（11.83±0.95）％],降低超氧化物歧化酶活性[（76.73±5.20）U/mgprot]、丙二醛[（371.82±23.05）nmol/mgprot]、活性氧（475.64±52.18）的含量,同时恢复细胞的活率[（74.31±5.53）％）]。结论1000μmol/L维生素C溶液不仅能促进人黑素细胞的增殖,对H2O2诱导的黑素细胞氧化应激损伤具有保护作用。     

The inhibition of free radical generation by human neutrophils through the synergistic effects of metronidazole with palmitoleic acid: a possible mechanism of action of metronidazole in rosacea and acne

Summary Metronidazole is clinically effective in treating not only rosacea but also acne inflammation. Yet it is generally considered not to be very effective in inhibiting the growth of anaerobic Propionibacterium acnes. We report here our investigation into the synergistic effects of metronidazole and palmitoleic acid on the anaerobic growth of P. acnes as well as on human neutrophil functions, including the generation of reactive oxygen species (ROS). Both metronidazole and palmitoleic acid, when used alone, only slightly inhibited the growth of P. acnes, and no significant decrease in human neutrophil functions, including the generation of ROS, was observed. But metronidazole used in the presence of palmitoleic acid markedly inhibited the anaerobic growth of P. acnes and decreased ROS generation by neutrophils. However, ROS generated in the xanthine-xanthine oxidase system were not affected. Metronidazole was shown to be clinically effective by decreasing neutrophil-generated ROS at the sites of inflammation with the aid of palmitoleic acid, which is generally present in human skin. By inhibiting oxidative tissue injury under in vivo conditions, treatment with metronidazole results in remarkable improvement of rosacea and acne.     

UV, sichtbares Licht, Infrarot

Experimental evidence suggests that the creation of free radicals – mainly reactive oxygen species (ROS) – is the common photobiological answer to the skin-sunlight interaction. The free radical action spectrum (wavelength dependency) for ultraviolet and visible light (280–700 nm) has been determined by quantitative ESR spectroscopy. Visible light produces around 50% of the total oxidative stress caused by sunlight. Reactive species like ^?O^- ₂, ^?OH and ^?CHR are generated by visible light. The amount of ROS correlates with the visible light intensity (illuminance). We demonstrated the creation of excess free radicals by near-infrared light (NIR, 700–1600 nm). Free radical generation does not depend exclusively on the NIR irradiance, but also on the NIR initiated skin temperature increase. The temperature dependence follows the physiological fever curve. Our results indicate that the complex biological system skin creates the same type of free radicals over the entire active solar spectrum. This general response will make it possible to define the beneficial or deleterious action of sunlight on human skin by introduction of a free radical threshold value.     

银杏叶提取物EGb761对氧化应激下白癜风黑素细胞抗氧化作用的影响

目的:明确银杏叶提取物(EGb761)对氧化应激下白癜风黑素细胞抗氧化作用的影响。方法:人正常黑素细胞系PIG1予以H2O2处理建立氧化应激模型,予以不同浓度(50μg/m L、100μg/m L、200μg/m L、300μg/m L、400μg/m L)EGb761处理,采用MTT法检测PIG1细胞活力,生物化学方法检测脂质过氧化代谢产物丙二醛(MDA)、乳酸脱氢酶(LDH),谷胱甘肽过氧化物酶活性及含量,流式细胞仪检测细胞内活性氧(ROS)水平。结果:与模型组比较,EGb761组PIG1细胞活力、SOD、GSHPx水平增高,ROS、MDA及LDH的表达水平降低。结论:银杏叶提取物EGb761可保护黑素细胞抵抗氧化应激损伤。     

SUCCESSFUL TREATMENT OF A PATIENT WITH RECURRENT FURUNCULOSIS BY VITAMIN C: IMPROVEMENT OF CLINICAL COURSE AND OF IMPAIRED NEUTROPHIL FUNCTIONS

Background. Neutrophils play a critical role in host defense against a variety of microbial pathogens. There is much information to suggest a role for vitamin C in the physiology of neutrophils. Thus, the effects of vitamin C treatment were studied in a patient with a history of recurrent furunculosis who showed altered neutrophil functions. Methods. Superoxide generation was measured by cytochrome C reduction. Phagocytosis of opsonized zymosan by neutrophils and chemotaxis on agarose plates were determined. Results. Chemotaxis, phagocytosis, and superoxide generation of the patient's neutrophils were significantly lower than those of the matched control. Treatment with vitamin C (500 mg/day) for 30 days caused a dramatic clinical response and a significant improvement of all three neutrophil functions to values similar to those of the controls. Conclusions. We suggest that the patient described here had a temporary defect in neutrophil functions. The treatment with vitamin C probably prevented neutrophil oxidation, thus contributing to recovery of neutrophil function and arrest of furunculosis.     

申克孢子丝菌酵母相与白念珠菌诱导中性粒细胞活性氧簇的差异性表达

目的 研究人中性粒细胞吞噬申克孢子丝菌酵母相和白念珠菌后胞内活性氧簇（ROS）的实时表达水平及对两者杀菌能力的差异。 方法 应用密度梯度离心法分离人外周血中性粒细胞,并通过ROS探针（DCFH-DA）、流式细胞仪和激光共聚焦显微镜检测申克孢子丝菌酵母相临床株和白念珠菌标准株ATCC 90028作用后,中性粒细胞内ROS的实时表达水平及对上述2种真菌孢子的杀菌率。 结果 申克孢子丝菌酵母相临床株和白念珠菌标准株ATCC 90028作用中性粒细胞60 min后,申克孢子丝菌组中性粒细胞内ROS表达水平达到峰值（平均荧光强度159.67 ± 11.34）,并显著高于白念珠菌组（112.22 ± 9.66）,经LSD-t检验,P < 0.01;而作用120 ～ 180 min后,胞内ROS表达水平（120 min为89.01 ± 9.81;180 min为57.63 ± 8.46）迅速下降,显著低于白念珠菌组中ROS的同期表达水平（120 min时为110.25 ± 7.28;180 min时为109.98 ± 9.00,经LSD-t检验,120 min时P < 0.05,180 min时P < 0.01）。激光共聚焦显微镜观察到,ROS主要表达于吞噬上述真菌孢子的中性粒细胞中,并被募集到被吞噬的部分孢子表面。中性粒细胞对申克孢子丝菌180 min杀菌率（19.21% ± 3.68%）亦显著低于其对白念珠菌孢子的杀菌率（26.63% ± 4.97%）,经LSD-t检验,P < 0.01。 结论 中性粒细胞吞噬上述2种真菌孢子后,胞内ROS呈明显的差异性表达。与白念珠菌相比,中性粒细胞内ROS水平的迅速下降在一定程度上抑制了其对申克孢子丝菌的杀伤效能。 【关键词】 孢子丝菌属; 念珠菌,白色; 中性白细胞; 活性氧     

Impaired neutrophil functions in patients with leukocytoclastic vasculitis

Background Leukocytoclastic vasculitis (LV) is characterized by segmental inflammation of small blood vessels, resulting in ischemic damage to the surrounding tissue. It is considered to be related to a type III hypersensitivity reaction, although the exact etiologic mechanism is not clear. Objective The purpose of this study was to evaluate neutrophil functions in patients with LV in order to understand their role in the pathogenesis of the disease. Methods Neutrophil functions were examined in 25 LV patients. The patients were divided into two groups: Group A consisted of 14 patients with drug-induced LV and Group B consisted of 11 patients where LV was induced by other factors. Results Both groups of patients showed significantly reduced chemotaxis and phagocytosis. Superoxide generation was significantly lower (P < 0.001) only in neutrophils from patients in Group A: 5.8 ± 0.5 nmoles O₂/10⁶ cells/min compared to 9.08 ± 0.8 nmoles O2/106 cells/min in the controls. Preincubation on normal neutrophils with the patients' sera caused an increase in their superoxide generation in accordance with the high IL-8 levels in these sera. Conclusions Neutrophil functions were significantly impaired in patients with LV. It is likely that factors present in LV plasma may chronically activate neutrophils, so that they become refracfory to further stimulation. Our study showed that neutrophil superoxide generation is low only in drug-induced LV; this test may assist in distinguishing such patients from those with LV induced by other causes.