Demonstration of Antigenic Sites in Glomeruli of Patients with Acute Poststreptococcal Glomerulonephritis by Immunofluorescein and Immunoferritin Technics

The presence and localization of antigenic sites in glomeruli of 14 patients with acute poststreptococcal glomerulonephritis (AGN) were studied by immunofluorescein and immunoferritin technics. Labeled IgG fractions from the same patients were used for the identification of antigenic sites. The staining capacity of these IgG fractions depended on the time when sera were obtained. Staining was minimal during the first week, and increased up to the fourth or fifth week. Glomeruli, however, stained only when renal tissue was obtained during the early phase of the disease. Precise localization of antigenic sites was determined with ferritin-conjugated patients' IgG. Segmental deposition of ferritin was observed in the mesangial matrix and on the endothelial side of the glomerular basement membrane. Subepithelial electron-dense deposits contained no or very few ferritin particles. In contrast, ferritin-conjugated antihuman IgG was distributed diffusely in the mesangial matrix, on the endothelial side of the basement membrane and in subepithelial deposits. These findings suggest that, during the early stage of acute poststreptococcal glomerulonephritis, free antigen is present in the glomeruli of patients with this disease.     

Roles of Lipoxin A4 in Preventing Paracetamol-Induced Acute Hepatic Injury in a Rabbit Model

The objective of this research is to investigate the potential role of lipoxin A4 in preventing paracetamol (PCM)-induced hepatic injury. One hundred male New Zealand white rabbits were randomly divided into control group, PCM group, N-acetylcysteine (NAC) group, lipoxin A4 (LXA4) group, and LXA4?+?NAC group. The rabbits were assigned to receive 300 mg/kg weight PCM in 0.9 % saline or equivalent volume of saline via gastric lavage. LXA4 (1.5 μg/kg) and equivalent volume of 2 % ethanol were separately given to the rabbits in LXA4-treated and PCM groups 24 h after PCM administration. Meanwhile, the rabbits in the NAC-treated groups received a loading dose of 140 mg/kg of N-acetylcysteine. The blood samples and liver tissue were collected for biochemical and histological evaluation 36 h after paracetamol administration. The administration of LXA4 24 h after paracetamol poisoning resulted in significant improvement in hepatic injury as represented by decrease of hepatocellular enzyme release and attenuation of hepatocyte apoptosis and necrosis. In LXA4-treated groups, the expression of TNF-α was significantly lower than those in PCM and NAC groups (p?<?0.05). In contrast, the level of IL-10 was significantly higher than PCM and NAC groups (p?<?0.05). Moreover, the expressions of NF-κB p65 in PCM and NAC groups were significantly increased compared with those of LXA4-treated groups and control group (respectively, p?<?0.05 and p?<?0.01). LXA4-treated groups also showed significantly higher survival rates. Lipoxin A4 significantly mitigates paracetamol-induced hepatic injury, in which anti-inflammation effect may play an important role, leading to hepatic apoptosis and necrosis.     

The role of Lipoxin A4 in endometrial biology and endometriosis

Lipoxin A₄ (LXA₄), an endogenous anti-inflammatory and immunomodulatory mediator studied in many disease states, is recently appreciated as a potentially significant player in the endometrium. This eicosanoid, synthesized from arachidonic acid via the action of lipoxygenase enzymes, is likely regulated in endometrial tissue during the menstrual cycle. Recent studies revealed that LXA₄ acts as an estrogen receptor agonist in endometrial epithelial cells, antagonizing some estrogen-mediated activities in a manner similar to the weak estrogen estriol, with which it shares structural similarity. LXA₄ may also be an anti-inflammatory molecule in the endometrium, though its precise function in various physiological and pathological scenarios remains to be determined. The expression patterns for LXA₄ and its receptor in the female reproductive tract suggest a role in pregnancy. The present review provides an oversight of its known and putative roles in the context of immuno-endocrine crosstalk. Endometriosis, a common inflammatory condition and a major cause of infertility and pain, is currently treated by surgery or anti-hormone therapies that are contraceptive and associated with undesirable side effects. LXA₄ may represent a potential therapeutic and further research to elucidate its function in endometrial tissue and the peritoneal cavity will undoubtedly provide valuable insights.     

脂氧素A4及其在炎症反应和免疫调节中的研究进展

脂氧素(LXs)是近三十年发现的一类含有三羟四烯结构的花生四烯酸合成产物,其中,脂氧素A4 (LXA4)是LXs家族的一员,近期研究表明其可对多种炎症细胞的功能和炎症相关基因的表达具有广泛调节作用,被称为炎症的“刹车信号”.然而,最新研究显示LXA4还与多种免疫细胞、免疫调节介质之间存在密切联系,且在机体的免疫调节过程中发挥重要作用.     

脂氧素A4抑制CTGF诱导的大鼠系膜细胞RANTES的产生

目的 了解结缔组织生长因子（CIEF）是否诱导肾小球系膜细胞产生趋化因子RANTES，了解脂氧素A4（LXA4）是否影响CTGF对合成RANTES的诱导作用，并探讨其作用机制。方法应用CTGF刺激培养的大鼠肾小球系膜细胞，应用RT-PCR方法测定RANTES的mRNA表达，应用ELISA测定上清液中RANTES。应用趋化试验测定上清液对单核细胞（THP-1）的趋化作用。应用Western blot测定分裂原激活的蛋白激酶（p42／44 MAPK）、磷脂酰肌醇3-激酶（P13-K）和蛋白激酶B（PKB）的表达。应用凝胶电泳迁移率试验测定核因子-kB（NF-kB）的表达。构建含脂氧素A4受体同源基因（LRHG）的真核表达载体pcDNA3.1／LRHG，并转染系膜细胞，观察LXA4,对CTGF作用的调节是否依赖LRHG。结果CTGF刺激使系膜细胞RANTES的mRNA表达与分泌量增加，增加磷酸化（P）-p42／44MAPK、P-PL3-K、P-PKB及NF-kB表达。LXA4呈剂量依赖性地抑制CTGF所致的上述变化。P-p42／44 MAPK抑制剂PD98059抑制CTGF诱导的p42／44 MAPK磷酸化与RANTES分泌。PI3-K抑制剂LY294002抑制CTGF诱导的PI3-K、PKB、NF-kB活化与RANTES分泌。NF-kB抑制剂PDTC抑制CTGF诱导的NF-kB活化与RANTES分泌。pcDNA3．1／LRHG转染使LXA4 对CTGF诱导的p42／44 MAPK磷酸化与RANTES的分泌的抑制作用增强。结论 LXA4可抑制CTGF引起的系膜细胞分泌RANTES，其机制依赖于抑制p42／44 MAPK、PI3-K／PKB的磷酸化与NF-kB活化。而LRHG转染细胞可增强LXA4的抑制作用，提示LRHG参与了LXA4的抑制作用。     

脂氧素A4抑制巴豆油所致小鼠外耳炎症

脂氧素A4(lipoxinA4,LXA4)为内源性脂类抗炎介质,被称为炎症的“刹车信号”[1]。虽然国外已报告LXA4可抑制实验性皮肤炎症,但其作用机制尚不清楚[2]。本文应用巴豆油制备小鼠的外耳炎症模型,探讨LXA4对炎症反应的作用及其机制。1材料与方法1·1耳廓炎症模型制备:实验用雌性昆明     

Acute Kidney Injury in Children after Hematopoietic Cell Transplantation Is Associated with Elevated Urine CXCL10 and CXCL9

Acute kidney injury (AKI) is nearly universally associated with worse outcomes, especially among children after hematopoietic stem cell transplant (HCT). Our objective was to examine urinary immune biomarkers of AKI after HCT to provide insights into novel mechanisms of kidney injury in this population. Studying patients undergoing allogeneic HCT provides a unique opportunity to examine immune markers of AKI because the risk of AKI is high and the immune system newly develops after transplant. Children (>2 years old) and young adults undergoing their first allogeneic HCT and enrolled in a prospective, observational cohort study at 2 large children's hospitals had urine collected pre-HCT and monthly for the first 4 months after HCT. Urine samples at each monthly time point were assayed for 8 immune-related biomarkers. AKI was defined as a 1.5-fold increase in the monthly serum creatinine value, which was recorded ±1 day from when the research urine sample was obtained, as compared with the pre-HCT baseline. Generalized estimating equation regression analysis evaluated the association between the monthly repeated measures (urinary biomarkers and AKI). A total of 176 patients were included from 2 pediatric centers. Thirty-six patients from 1 center were analyzed as a discovery cohort and the remaining 140 patients from the second center were analyzed as a validation cohort. AKI rates were 18% to 35% depending on the monthly time point after HCT. Urine CXCL10 and CXCL9 concentrations were significantly higher among children who developed AKI compared with children who did not (P < .01) in both cohorts. In order to gain a better understanding of the cellular source for these biomarkers in the urine, we also analyzed in vitro expression of CXCL10 and CXCL9 in kidney cell lines after stimulation with interferon-γ and interferon-α. HEK293-epithelial kidney cells demonstrated interferon-induced expression of CXCL10 and CXCL9, suggesting a potential mechanism driving the key finding. CXCL10 and CXCL9 are associated with AKI after HCT and are therefore promising biomarkers to guide improved diagnostic and treatment strategies for AKI in this high-risk population.     

The Effect and Mechanism of Lipoxin A4 on Neutrophil Function in LPS-Induced Lung Injury

Inflammation - Excessive inflammatory response caused by infiltration of a large number of neutrophils is one of the important features of acute lung injury (ALI)/acute respiratory distress...     

急性肾小球肾炎尿IgG测定的临床研究

目的探讨小儿急性肾小球肾炎(AGN)尿IgG测定的临床意义. 方法用免疫比浊法测定 32例 AGN患儿急性期和恢复期的尿IgG,比较两者尿IgG的阳性率.同时应用LOGISTIC多元回归分析急性期尿IgG与血尿、浮肿、高血压、BUN和年龄的相关关系. 结果急性期尿IgG阳性率为78%,比恢复期31%明显增高,χ2=14.19,p<0.005,急性期尿IgG与血尿、浮肿、高血压、BUN和年龄无相关关系. 结论 AGN患儿尿IgG阳性反映肾小球滤过膜通透性明显增加,可考虑作为活动的指标之一,但与病情的轻重程度无关.     

12/15-Lipoxygenase during the regulation of inflammation, immunity, and self-tolerance

12/15-Lipoxygenase (12/15-LO) catalyzes the oxidation of free and esterified fatty acids thereby generating a whole spectrum of bioactive lipid mediators. This enzyme is involved in the regulation of various homeostatic processes as well as in the pathogenesis of multiple diseases. During the innate and adaptive immune response, 12/15-LO and its products exert both pro- and anti-inflammatory effects. Likewise, this enzyme has been implicated in the pathogenesis of autoimmune disease as well as in the maintenance of self-tolerance. This review will summarize our current knowledge about the role of 12/15-LO and will try to examine the two faces of this enzyme within the context of inflammation and immunity.     

急性肾小球肾炎尿IgG测定的临床研究

目的：探讨小儿急性肾小球肾炎（AGN）尿IgG测定的临床意义。方法：用免疫比浊法测定32例AGN患儿急性期和恢复期的尿IgG，比较两者尿IgG的阳性率。同时应用LOGISTIC多元回归分析急性期尿IgG与血尿、浮肿、高血压、BUN和年龄的相关关系。结果：急性期尿IgG阳性率为78％，比恢复期31％明显增高，χ^2=14.19,p＜0．005，急性期尿IgG与血尿、浮肿、高血压、BUN和年龄无相关关系。结论：AGN患儿尿IgG阳性反映肾小球滤过膜通透性明显增加，可考虑作为活动的指标之一，但与病情的轻重程度无关。     

Effect of Lipoxin A4 on Myocardial Ischemia Reperfusion Injury Following Cardiac Arrest in a Rabbit Model

In the present study, we investigated the effect of lipoxin A4 on myocardial ischemia–reperfusion injury (IRI) following cardiac arrest (CA) in a rabbit model. Lipoxin A4 is a metabolite of arachidonic acid in the eicosanoid, it is called “brake signal” for its anti-inflammatory activity. Some inflammatory factors (IL-1β, IL-6, TNF-α, and IL-10), NF-κB p65, infarct ratios, apoptotic index, cardiac troponin I (cTnI), hemodynamic and myocardial structures were measured or observed in different groups. Lipoxin A4 inhibits the expression of IL-1β, IL-6, and TNF-α, the values of the infarct ratios, apoptotic index, the level of serum cTnI and NF-κB p65. Meanwhile, it improves the expression of IL-10, hemodynamic, myocardial structure, and function. These indicate that lipoxin A4 mitigates postresuscitation myocardial IRI in which anti-inflammation and suppression of NF-κB activation may play an important role.