雾化吸入灭活草分枝杆菌降低哮喘小鼠核因子κB及细胞间黏附分子1的表达

 目的:研究雾化吸入灭活草分枝杆菌对支气管哮喘小鼠气道炎症,以及哮喘肺组织中核因子κB(NF-κB)、细胞间黏附分子1(ICAM-1)和血管细胞黏附分子1(VCAM-1)的影响,探讨雾化吸入灭活草分枝杆菌防治哮喘的机制。方法:将24只雄性BALB/c小鼠按随机数字表法分为3组,每组8只：正常对照组（A）、哮喘模型组（B）和治疗组（C）。以鸡卵清蛋白致敏制造小鼠支气管哮喘模型。C组在激发后给予雾化吸入灭活草分枝杆菌治疗5 d,每天1次。各组动物处死后提取肺组织和支气管肺泡灌洗液（BALF）。进行病理HE染色及AB-PAS染色观察气道炎症浸润及黏液分泌情况,并行病理半定量分析。对BALF中炎症细胞进行分类计数。实时荧光定量PCR检测肺组织NF-κB、ICAM-1和VCAM-1的mRNA表达水平。结果:治疗组嗜酸性粒细胞比例低于模型组(P<0.05),气道炎症病变及黏液分泌情况较模型组减轻(P<0.05, P<0.01)。哮喘模型组的肺组织中NF-κB mRNA含量与正常组相比显著升高(P<0.01),而治疗组肺组织中的NF-κB mRNA 含量明显低于模型组(P<0.05);模型组的ICAM-1 mRNA 水平比正常组高(P<0.05),但治疗后明显降低(P<0.01);VCAM-1的 mRNA水平在各组间无显著差异。相关性检验发现小鼠肺组织中VCAM-1的mRNA与ICAM-1的mRNA呈明显正相关(r=0.84,P<0.01),但NF-κB的mRNA与ICAM-1的mRNA、VCAM-1的mRNA无明显相关性(均P>0.05)。结论:雾化吸入草分枝杆菌对支气管哮喘小鼠气道炎症及黏液分泌有抑制作用;NF-κB参与哮喘发病过程,雾化吸入灭活草分枝杆菌降低哮喘小鼠的NF-κB水平。同时雾化吸入灭活草分枝杆菌可降低黏附分子尤其是ICAM-1的表达,是其控制炎症的另一个重要机制。     

Increased PSGL-1 expression on granulocytes from allergic-asthmatic subjects results in enhanced leukocyte recruitment under flow conditions

Allergic asthma is increasing in incidence and severity in many industrial countries. Leukocyte recruitment into the airways of affected individuals contributes to the severity of the disease. In this study, whole blood from normal, allergic, asthmatic, or allergic-asthmatic subjects was perfused over immobilized adhesion molecules using an in vitro flow chamber system to determine if there were differences in leukocyte recruitment in these patient populations. Leukocytes from allergic-asthmatic subjects showed a threefold increase in recruitment on P-selectin as compared with normal controls. In both patient populations, the accumulated cells were exclusively neutrophils and eosinophils. Increased granulocyte recruitment was specific for P-selectin, as neither purified E-selectin nor vascular cell adhesion molecule-1 (VCAM-1) supported enhanced leukocyte recruitment from allergic-asthmatics. Leukocyte accumulation on P-selectin was completely blocked by an anti-P-selectin or anti-P-selectin glycoprotein ligand-1 (PSGL-1) monoclonal antibody. Flow cytometry revealed that neutrophils and eosinophils from allergic-asthmatic subjects had increased expression of PSGL-1, whereas expression of another adhesion molecule, L-selectin, was unchanged. PSGL-1 expression on peripheral blood mononuclear cells of allergic-asthmatic patients was unaffected. The increased PSGL-1 expression on granulocytes from allergic-asthmatic patients also led to enhanced leukocyte recruitment on interleukin-4-stimulated human umbilical vein endothelial cells, which express P-selectin and VCAM-1. Thus, increased PSGL-1 expression on granulocytes from allergic-asthmatic subjects resulted in increased leukocyte recruitment on P-selectin under flow conditions.     

Airway responsiveness to acetaldehyde in patients with asthma: relationship to methacholine responsiveness and peak expiratory flow variation

BACKGROUND: Although airway hyperresponsiveness to inhaled acetaldehyde has been documented in Japanese patients with asthma, the response to this bronchoconstrictor agent has never been studied in Caucasians. OBJECTIVES: The objectives of the study were to determine differences in airway responsiveness to acetaldehyde between asthmatic and healthy subjects, and to examine the relationship between acetaldehyde responsiveness and the variability of peak expiratory flow (PEF). METHODS: The response to methacholine and acetaldehyde challenges was measured in 81 non-smoking adults (61 asthmatics and 20 normal controls). Subjects recorded PEF morning and evening for 14 days. The response to both bronchoconstrictor agents was measured by the PC20 (provocative concentration required to produce a 20% fall in FEV1). PEF variation was expressed as amplitude percentage mean, and as low percentage best (lowest PEF expressed as a percentage of the best PEF recorded). RESULTS: The two types of challenge yielded a similarly high level of sensitivity (100% for methacholine and 92% for acetaldehyde) and specificity (90 and 100%, respectively) to distinguish between asthma and controls. Asthmatic subjects were on average 265-fold less sensitive to acetaldehyde than to methacholine. PC20 acetaldehyde correlated weakly but significantly with both indices of PEF variation (amplitude percentage mean: rho = - 0.36, P = 0. 004; low percentage best: rho = 0.42, P = 0.001). CONCLUSIONS: These results indicate that airway hyperresponsiveness to acetaldehyde is a sensitive and specific indicator for separating asthmatic and normal subjects. Airway responsiveness to methacholine or acetaldehyde and PEF variation are not reflecting the same pathophysiological process in the airways.     

Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways

BACKGROUND: Allergic rhinitis (AR) and asthma are characterized by means of a similar inflammatory process in which eosinophils are important effector cells. The migration of eosinophils from the blood into the tissues is dependent on adhesion molecules. OBJECTIVE: To analyze the aspects of nasobronchial cross-talk, we studied the expression of adhesion molecules in nasal and bronchial mucosa after nasal allergen provocation (NP). METHODS: Nine nonasthmatic subjects with seasonal AR and 9 healthy control subjects underwent NP out of season. Bronchial and nasal biopsy specimens were taken before (T(0)) and 24 hours after NP (T(24)). Mucosal sections were analyzed for the presence of eosinophils, IL-5, eotaxin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and human endothelium (CD31). RESULTS: At T(24), an influx of eosinophils was detected in nasal epithelium (P =.01) and lamina propria (P <.01), as well as in bronchial epithelium (P =.05) and lamina propria (P <.05), of the patients with AR. At T(24), increased expression of ICAM-1, as well as increased percentages of ICAM-1+, VCAM-1+, and E-selectin+ vessels, were seen in nasal and bronchial tissue of patients with AR. The number of mucosal eosinophils correlated with the local expression of ICAM-1, E-selectin, and VCAM-1 in patients with AR. CONCLUSION: This study shows that NP in patients with AR results in generalized airway inflammation through upregulation of adhesion molecules.     

Adhesion molecules in atopic dermatitis: VCAM-1 and ICAM-1 expression is increased in healthy-appearing skin

In the skin of normal and atopic individuals, the expression of E-selectin (ELAM-1), L-selectin (LECAM-1), P-selectin (CD62), CD31 (PECAM), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and cutaneous lymphocyte antigen (CLA) were compared by immunostaining of skin biopsies which were taken from normal individuals ( n = 17), the healthy-appearing skin of patients with atopic dermatitis ( n = 10), and their acute ( n = 5) and chronic ( n = 6) skin lesions. In contrast to ELAM-1, the expression of VCAM-1 and ICAM-1 was found to be significantly increased in nonlesional atopic skin in comparison to the skin of normal individuals. Moreover, in contrast to normal skin of healthy individuals, nonlesional atopic skin showed a further increase of VCAM-1, ICAM-1, and ELAM-1 when cultured with medium alone. This suggests that certain adhesion molecules are constitutively upregulated in healthy-appearing skin of patients with atopic dermatitis. In addition, atopic skin appears to respond to nonspecific stimuli (such as culture with medium alone) with upregulation of VCAM-1, ICAM-1, and ELAM-1. It is suggested that the observed upregulation of adhesion molecules is mediated by the release of cytokines such as interleukin-4 from cells which reside in atopic skin. The question of whether the inherent upregulation of adhesion molecules in atopic skin contributes to the development of Th2 cells, which have been found to predominate in atopic inflammation, has to be further investigated.     

轻度修饰低密度脂蛋白对血管内皮细胞粘附功能影响及其机理初探

目的:观察轻度修饰LDL(MM-LDL)对培养人脐静脉内皮细胞(HUVEC)与人类单核细胞系U937粘附功能及其表面粘附分子表达的影响。方法:利用计数法观察经MM-LDL作用的HUVEC与U937细胞的粘附率;用ELISA方法检测MM-LDL作用后HUVEC膜表面粘附分子血管细胞粘附分子-1(VCAM-1)、细胞间粘附分子-1(ICAM-1)及P选择素(P-selectin)的表达。结果:MM-LDL(75mg/L)作用HUVEC4h后,其对U937细胞粘附率明显增加(P<0.01),HUVEC膜表面未见VCAM-1,ICAM-1,P-selectin表达上调,作为阳性对照重组肿瘤坏死因子α(rTNF_α)5.0μg/L可显著诱导以上3种粘附分子表达。延长MM-LDL与HUVEC作用时间至18h可诱导产生P-selectin表达,对VCAM-1表达无影响。结论:MM-LDL诱导的HUVEC与U937粘附不是通过ICAM-1、VCAM-1介导的,P-selectin可能起一定的作用。     

Biological function of CD40 on human endothelial cells: costimulation with CD40 ligand and interleukin-4 selectively induces expression of vascular cell adhesion molecule-1 and P-selectin resulting in preferential adhesion of lymphocytes

The expression of adhesion molecules on vascular endothelial cells determines the pattern of migration and extravasation of leucocytes in inflammation and immunity. Here we show that costimulation with CD40 ligand (CD40L) and interleukin (IL)-4 (or IL-13) gives rise to a unique pattern of adhesion molecule expression by human umbilical vein endothelial cells (HUVEC). CD40 ligation alone enhanced expression of vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and E-selectin whereas IL-4 and IL-13 increased expression of VCAM-1 and P-selectin but not ICAM-1 or E-selectin. When IL-4 and CD40L were combined there was an additional increase of both VCAM-1 and P-selectin, but ICAM-1 and E-selectin were both inhibited. The combined effects of IL-4 and CD40L signalling were not the result of altered response kinetics, enhanced sensitivity of the endothelium, or increased expression of CD40 or the IL-4 receptor. The rise in VCAM-1 expression induced by combined IL-4 and CD40L stimulation was slower and more sustained than with tumour necrosis factor-alpha (TNF-alpha) and occurred only on a subset (75-80%) of the endothelial cell population compared to 100% with TNF-alpha. Costimulation with IL-4 and CD40L increased adhesion of T cells and B cells above levels obtained with either signal alone, but decreased adhesion of neutrophils. Furthermore, CD40 and IL-4 synergistically increased IL-6 but decreased IL-8 production by HUVEC. These results show that interactions between IL-4 and CD40 on endothelial cells give rise to specific patterns of adhesion molecule expression and cytokine production that may have important implications for lymphocyte and neutrophil migration and function at sites of inflammation.     

Urokinase-type plasminogen activator modulates airway eosinophil adhesion in asthma

Eosinophils migrate from the vascular circulation to the inflamed airways during asthma exacerbations. While the mechanism(s) of this process is not known, the expression of urokinase-type plasminogen activator receptor (uPAR) has been found to modulate neutrophil adhesion and migration to inflammatory sites. We hypothesized that increased expression of uPAR and its ligand, uPA, enhance eosinophil adhesion in patients with asthma. Patients with allergic asthma underwent segmental bronchoprovocation with allergen; 48 h later, peripheral blood and airway (from bronchoalveolar lavage fluid) eosinophils were isolated. uPA and uPAR protein expression were measured by flow cytometry and Western blot; mRNA was quantified by real-time PCR. Eosinophil adhesion to intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 was assessed by eosinophil peroxidase activity. Airway eosinophils expressed significantly more uPA and uPAR protein and uPAR mRNA than peripheral blood eosinophils. Removal of cell-bound uPA and/or addition of exogenous uPA had no effect on blood eosinophil adhesion to ICAM-1 or VCAM-1. In contrast, exogenous uPA stimulated ICAM and VCAM adhesion of airway eosinophils. N-formyl-methionyl-leucyl-phenylalanine-activated airway eosinophil adherence to VCAM-1 and ICAM-1 (VCAM-1, 52.8 +/- 4.7%; ICAM-1, 49.2 +/- 5.3%) was increased over blood eosinophil adhesion (VCAM-1, 38.4 +/- 3.6%; ICAM-1, 27.7 +/- 4.9%; P < 0.05). Removal of cell-bound uPA from airway eosinophils decreased adhesion to blood cell levels; reintroduction of exogenous uPA completely restored adhesion levels. These data suggest that constitutive uPA primes, and exogenous uPA can activate, airway eosinophil adhesion following segmental allergen challenge and that increased uPA expression may be a mechanism of increased eosinophil infiltration and function in asthma.     

Apoptosis and loss of adhesion of bronchial epithelial cells in asthma

BACKGROUND: Asthma is an inflammatory airway disease associated with infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (EC). We have recently shown that T cells and eosinophils cooperate in inducing bronchial EC apoptosis in asthma through secretion of IFN-gamma and TNF-alpha. Since EC shedding is a histologic hallmark of asthma, the intercellular junction of EC may be a target of pro-inflammatory cytokines. METHODS: Bronchial EC, cultured and exposed to IFN-gamma and TNF-alpha, were studied for the expression of adhesion molecules and apoptosis. In addition, the epithelial layer of bronchial biopsies from asthma patients was evaluated for apoptosis, shedding, and expression of adhesion molecules. RESULTS: We demonstrate that the induction of EC apoptosis is accompanied by loss of E-cadherin. In situ examination of E-cadherin in asthma revealed a reduction in its expression on EC membranes. In contrast, the in vitro and in vivo expression of beta1-integrins and intercellular adhesion molecule-1 (ICAM-1) increased on EC during asthmatic airway inflammation. CONCLUSIONS: Loss of cadherin-mediated intercellular adhesion and apoptosis could account for fragility and shedding of EC in asthma, especially since this occurs between columnar and basal EC.     

流体切应力对内皮细胞粘附分子表达的影响

在动脉粥样硬化(Atherosclerosis,As)的发生发展中各种白细胞,包括单核细胞对内皮细胞的粘附可能起着较为重要的作用。在体内,血流切应力对内皮细胞的形态和功能有重要影响。为了阐明流体切应力对内皮细胞表面粘附分子表达的影响,本文研究了流体切应力(2.23～6.08dyne/cm     

The role of fibronectin in bronchoalveolar lavage fluid of asthmatic patients

Allergic and chronic inflammation of the airway is regarded as the main pathogenesis of bronchial asthma, in which adhesion of inflammatory cells requires the expression of adhesion molecules. Thus, to clarify the role of fibronectin (FN) in the airway inflammation of bronchial asthma, FN levels in plasma and bronchoalveolar lavage fluid (BALF) from bronchial asthmatics were determined. FN concentrations in plasma and BALF were measured by enzyme-linked immunosorvent assay (ELISA) in 17 asthmatic patients and 10 healthy controls to elucidate the role of FN in allergic inflammation. The mean FN/albumin (Alb) level in the BALF of asthmatic patients was 2.973 micrograms/mg, which was significantly higher than that of healthy controls (0.727 microgram/mg). Non-atopic asthmatics showed a significantly higher level of FN in their BALF in comparison with atopic asthmatics, although the ratio of FN to albumin showed no significant difference. FN levels in BALF correlated significantly with total cell density (r = 0.71, P < 0.05) and alveolar macrophage density (r = 0.64, P < 0.05). FN levels in plasma did not correlate with those in BALF. In conclusion, increased FN in BALF, which was produced locally in the airways of asthmatic patients, is actively involved in the regulation of allergic inflammation.     

Immunohistopathological appearance of three different types of injury in human skin

OBJECTIVE AND DESIGN: To determine whether underlying mechanisms of inflammation, like cellular infiltrates, expression of adhesion molecule and cytokine patterns are similar under different conditions of injury. Skin biopsies were taken of three different groups of patients in which local inflammation of the skin might occur. MATERIAL, PATIENTS: Skin activation was studied as a result of incision during surgery under aseptic conditions, as a result of a local bacterial infection and as a result of blunt trauma, resulting in a femoral fracture, without disruption of the epithelial barrier. METHODS: Skin biopsies were snap frozen for immunohistochemical analysis. RESULTS: Incision of the skin resulted in a granulocyte infiltrate, paralleled by E-selectin expression. As a result of infection granulocytes were observed and monocyte/macrophage and T cell numbers were increased. Furthermore, E-selectin, VCAM-1 and ICAM-1 expression increased and cytokine expression markedly changed compared to normal skin. Skin taken at the site of the femoral fracture showed no signs of inflammation. CONCLUSION: Different stimuli lead to different local inflammatory responses in human skin.     

Expression of VCAM-1, ICAM-1, E- and P-selectin and tumour-associated macrophages in renal cell carcinoma

AIMS: Neoangiogenesis is accompanied by an increase in endothelial surface, which can support infiltration by immune cells depending on adhesion molecule expression. Therefore, the expression of cell adhesion molecules on microvessels and epithelial cells was analysed in renal cell carcinomas as compared to tumour-free tissue. METHODS AND RESULTS: PECAM-1, CD34, ICAM-1, VCAM-1, VLA-4, P- and E-selectin, the macrophage antigens Ki-M1P and Mac-1, and lymphocyte function antigen LFA-1 were identified immunohistochemically. VCAM-1, ICAM-1, and E-selectin were equally or less expressed, whereas P-selectin was increased on microvessels in tumour tissue. The density of VCAM-1-positive tumour microvessels correlated positively with an advanced tumour stage and E- and P-selectin-positive tumour microvessels with the amount of associated macrophages. The expression of ICAM-1 and VCAM-1 on neoplastic epithelia correlated with an increased density of macrophages and a minor degree of tumour differentiation. CONCLUSIONS: The positive correlation of macrophage infiltration and expression of cell adhesion molecules on tumour microvessels and epithelia with minor tumour differentiation and an advanced stage indicates that adhesion molecule expression is not associated with an effective antitumour function of macrophages     

Cyclic-strain-induced endothelial cell expression of adhesion molecules and their roles in monocyte-endothelial interaction.

Vascular endothelial cells (ECs) are constantly subjected to hemodynamic forces that may regulate monocyte-endothelial interaction in vivo. To examine the effects of cyclic strain on endothelial expression of monocyte adhesion molecules, E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) ECs were exposed to physiologically relevant levels of cyclic strain. When ECs were under 25% maximal strain at 30 cycles/min for 24 h, the expression of E-selectin significantly (p<0.05) increased, by 83%, compared to control ECs under static conditions. Similarly, monocyte adhesion to ECs under strain (maximum of 15 or 25% at 30 and 60 cycles/min for 24 h) also significantly (p<0.05) increased, by >82%. This cyclic-strain-induced monocyte adhesion was substantially inhibited (83.5%) by anti-E-selectin antibody. ICAM-1 expression also significantly increased, by 62%, when ECs were under 25% maximal strain at 30 cycles/min for 3 h whereas VCAM-1 expression by ECs under strain (for 0.5, 3, and 24 h) did not change compared to static ECs. When ECs were treated with anti-ICAM-1 antibody and monocytes with anti-VLA-4 antibody, an increase in monocyte adhesion to ECs under cyclic strain was reduced significantly. These results demonstrate that cyclic strain can induce EC expression of monocyte adhesion molecules E-selectin, ICAM-1, and VCAM-1 in a time-dependent manner and thus can mediate monocyte adhesion.     

Patterns of myocardial cell adhesion molecule expression in human endomyocardial biopsies after cardiac transplantation. Induced ICAM-1 and VCAM-1 related to implantation and rejection.

Conflicting patterns of myocardial cell adhesion molecule expression associated with cardiac rejection have emerged from numerous studies of randomly selected cardiac biopsies. We designed a prospective, longitudinal study which reports both qualitative and quantitative levels of myocardial ICAM-1, VCAM-1, E-selectin, and P-selectin expression in sequential human cardiac allograft biopsies. Intense ICAM-1 and VCAM-1 staining was found in all biopsies during the first three weeks after transplant and coincided with elevated serum levels of troponin T, a sensitive marker of ischemic myocyte injury. Baseline ICAM-1 and VCAM-1 expression returned within three to four weeks, as did serum troponin T levels in all patients who did not develop rejection. All 29 rejection episodes encountered were associated with intense ICAM-1 staining, while 24 of the 29 (83%) had intense VCAM-1 staining. Increased ELAM-1 and CD62 staining was only rarely observed. Persistence of increased ICAM-1 and VCAM-1 staining after treated rejection episodes predicted a recurrent rejection episode within two months (75% positive and 100% negative predictive value). Objective quantitative measurements by radioimmunoassay (RIA) confirmed these patterns of induced ICAM-1 and VCAM-1 expression. Thus, longitudinal monitoring of serial biopsies for myocardial ICAM-1 and VCAM-1 expression could be useful in the early detection of rejection episodes and monitoring the efficacy of immunosuppressive therapy.     

Airway cell and cytokine changes in early asthma deterioration after inhaled corticosteroid reduction

BACKGROUND: Back-titration of inhaled corticosteroid (ICS) dose in well-controlled asthma patients is emphasized in clinical guidelines, but there are few published data on the airway cell and cytokine changes in relation to ICS reduction. In our study, 20 mild-to-moderate persistent (inspite of low-moderate dose ICS treatment) asthmatic subjects prospectively rendered largely asymptomatic by high-dose ICS were assessed again by clinical, physiological, and airway inflammatory indices after 4-8 weeks of reduced ICS treatment. We aimed at assessing the underlying pathological changes in relation to clinical deterioration. METHODS: Patients recorded daily symptom scores and peak expiratory flows (PEF). Spirometry and airways hyperreactivity (AHR) were measured and bronchoscopy was performed with assessment of airway biopsies (mast cells, eosinophils, neutrophils, and T lymphocytes), bronchoalveolar lavage (BAL) IL-5 and eotaxin levels and cellular profiles at the end of high-dose ICS therapy and again after ICS dose reduction. Baseline data were compared with symptomatic steroid-free asthmatics (n=42) and non-asthmatic controls (n=28). RESULTS: After ICS reduction, subjects experienced a variable but overall significant increase in symptoms and reductions in PEF and forced expiratory volume in 1 s. There were no corresponding changes in AHR or airways eosinophilia. The most relevant pathogenic changes were increased CD4(+)/CD8(+) T cell ratio, and decreased sICAM-1 and CD18 macrophage staining (potentially indicating ligand binding). However, there was no relationship between the spectrum of clinical deterioration and the changes in cellular profiles or BAL cytokines. CONCLUSIONS: These data suggest that clinical markers remain the most sensitive measures of early deterioration in asthma during back-titration of ICS, occurring at a time when AHR and conventional indices of asthmatic airway inflammation appear unchanged. These findings have major relevance to management and to how back-titration of ICS therapy is monitored.     

Fibroblast-eosinophil interaction: modulation of adhesion molecules expression and chemokine release by human fetal lung fibroblasts in response to IL-4 and TNF-alpha

In addition to be involved in airway remodelling observed in asthmatic patients, lung fibroblasts may directly contribute to pulmonary inflammation through the release of mediators and through the expression of surface molecules involved in cell-cell interaction. The aim of the study was to evaluate whether two cytokines involved in asthma pathogenesis, IL-4 and TNF-alpha, could modulate the expression of adhesion molecules (VCAM-1 and ICAM-1) and the secretion of chemokines (eotaxin and MCP-1) related to eosinophil recruitment and activation. The constitutive expression of VCAM-1 by unstimulated fibroblasts was over 2-fold lower than that of ICAM-1 (P<0.05). Significant differences were also observed in the release of chemokines by unstimulated fibroblast, the levels of eotaxin being over 17-fold lower than those of MCP-1. Stimulation of the cells with IL-4 or TNF-alpha induced a dose-dependent increase in VCAM-1, while ICAM-1 was overexpressed only in culture stimulated by TNF-alpha (P<0.05) but not in those exposed to IL-4 (P>0.05 each comparison). In contrast, a significant increase in MCP-1 and eotaxin release was observed in the presence of TNF-alpha (P<0.05) but not of IL-4 (P>0.05). These data show that two 'proinflammatory' cytokines, such as IL-4 and TNF-alpha, may have different and complementary effects on functions involved in the cross-talking between fibroblasts and eosinophils.     

异鼠李素抑制卵清蛋白诱导的哮喘小鼠肺部炎症

目的:探讨异鼠李素对哮喘模型小鼠肺炎的影响并初步分析其机制.方法:将32只BALB/c小鼠随机分为正常对照组、哮喘模型组、异鼠李素低剂量(50 mg/kg)治疗组和异鼠李素高剂量(150 mg/kg)治疗组.利用卵清蛋白(ovalbumin,OVA)构建小鼠哮喘模型.HE染色和PAS染色观察肺组织病理学变化;ELISA...     

Endothelium injury and inflammatory state during abdominal aortic aneurysm surgery: scrutinizing the very early and minute injurious effects using endothelial markers – a pilot study

Introduction

One of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Acute kidney injury is an inflammatory process whose pathogenesis involves endothelial cells (EC). The aim of this study was to assess the dynamics of endothelium injury markers measured during elective AAA surgery which might confirm the inflammatory character of AKI.

Material and methods

The study group consisted of 14 patients with AAA. We measured plasma soluble forms of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin as well as the levels of von Willebrand factor (vWF) before, during (including intra-abdominal vein levels before and after aortic clamp removal) and within 2 days after surgery.

Results

We have found a biphasic response of ICAM-1, VCAM-1 and P-selectin with an initial fall and subsequent rise. However, only VCAM-1 changes were significant compared to its baseline value. The maximum decrease of VCAM-1 was observed in the renal vein 5 min after aortic clamp removal (335.42 ±129.63 ng/ml vs. 488.90 ±169.80 ng/ml baseline value, p < 0.05), and the highest rise 48 h after aortic clamp removal (721.46 ±333.99 vs. baseline, p < 0.05).

Conclusions

Vascular cell adhesion molecule-1 turned out to be the most sensitive indicator of EC injury and inflammatory status after AAA surgery. During AAA surgery, soluble forms of P-selectin, ICAM-1 and VCAM-1 demonstrate a biphasic response with an initial fall and subsequent rise. These soluble forms could have a modulatory effect on the development of inflammation.