Intrauterine undernutrition in rats interferes with leukocyte migration, decreasing adhesion molecule expression in leukocytes and endothelial cells

Experimental and epidemiologic data have shown that malnutrition predisposes individuals to infections. Immune responses are compromised, particularly in undernourished children. Therefore, we investigated the migratory capacity of leukocytes, using the intravital microscopy technique, in male Wistar rats (8-9 wk of age) that were undernourished in utero after their dams were fed 50% less food than the amount consumed by control dams. The number of leukocytes rolling along the venular endothelium, sticking after stimulation with leukotriene B4, tumor necrosis factor-alpha (TNF-alpha) or zymosan-activated plasma, or migrating after TNF-alpha stimulation was significantly reduced in the undernourished rat offspring. Compared with nourished rat offspring, undernourished offspring had significantly reduced numbers of circulating leukocytes, higher blood pressure, and higher leukocyte rolling velocity (V(WBC)), as well as a higher ratio between V(WBC) and RBC velocity (V(RBC)). Endothelial P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression, analyzed by immunohistochemistry, and basal leukocyte L-selectin expression, analyzed by flow cytometry, were significantly reduced in the undernourished rat offspring. Because the groups did not differ in leukocyte CD11/18 expression, endothelial expression of platelet-endothelial cell adhesion molecule-1, or venular blood flow velocity and, consequently, venular shear rate, we conclude that intrauterine undernutrition in rats reduces leukocyte migration, downregulates endothelial expression of P-selectin and ICAM-1, as well as leukocyte expression of L-selectin, while reducing leukocyte counts. The higher V(WBC) and V(WBC)/V(RBC) ratio may also play a role in this reduced leukocyte migration. Our data suggest that this phenomenon is involved in the increased predisposition to infections in undernourished subjects.     

Conjugated linoleic acid isomers may diminish human macrophages adhesion to endothelial surface

Dysfunction of endothelial cells and activation of monocytes in the vascular wall are important pathogenetic factors of atherosclerosis. Conjugated linoleic acids (CLAs) can modulate the function of immune system in humans: reduce the concentration of atherogenic lipoproteins, and the intensity of inflammatory processes in the plasma. In this paper, we focus on macrophage's surface integrins (β1 integrin CD49d/CD29-(VLA4); Mac-1 as well as endothelial human vein endothelial cell (HUVEC) surface adhesins: vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1)) expression in relation to CLA isomer used during cell culture. Both CLA isomers decreased expression of VLA-4 and Mac-1 on macrophages compared with control cells (cultured with bovine serum albumine (BSA) or oxidized form of low-density lipoproteins). cis-9, trans-11 CLA isomer reduced ICAM-1 and VCAM-1 expression on the endothelium surface. Strong tendency to reduce of adhesion of macrophages to HUVEC in the cells cultured with CLA isomers was observed. The potential role of cis-9, trans-11 CLA in the reduction of adhesion of macrophages to the HUVEC – one of the important steps in the inflammatory process, can be considerate. These mechanisms may contribute to the potent anti-atherosclerotic effects of CLA in vivo.     

Conjugated linoleic acid isomers may diminish human macrophages adhesion to endothelial surface

Dysfunction of endothelial cells and activation of monocytes in the vascular wall are important pathogenetic factors of atherosclerosis. Conjugated linoleic acids (CLAs) can modulate the function of immune system in humans: reduce the concentration of atherogenic lipoproteins, and the intensity of inflammatory processes in the plasma. In this paper, we focus on macrophage's surface integrins (β1 integrin CD49d/CD29-(VLA4); Mac-1 as well as endothelial human vein endothelial cell (HUVEC) surface adhesins: vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1)) expression in relation to CLA isomer used during cell culture. Both CLA isomers decreased expression of VLA-4 and Mac-1 on macrophages compared with control cells (cultured with bovine serum albumine (BSA) or oxidized form of low-density lipoproteins). cis-9, trans-11 CLA isomer reduced ICAM-1 and VCAM-1 expression on the endothelium surface. Strong tendency to reduce of adhesion of macrophages to HUVEC in the cells cultured with CLA isomers was observed. The potential role of cis-9, trans-11 CLA in the reduction of adhesion of macrophages to the HUVEC--one of the important steps in the inflammatory process, can be considerate. These mechanisms may contribute to the potent anti-atherosclerotic effects of CLA in vivo.     

Expression of intercellular adhesion molecule-1 (ICAM-1) in choriodecidua with labour and delivery at term and preterm

To evaluate the association between intercellular adhesion molecule-1 (ICAM-1) in the choriodecidua and preterm labour and delivery, ICAM-1 mRNA abundance was assessed by northern analysis, and protein levels by ELISA, in samples of this tissue after term and preterm delivery. The median ICAM-1 mRNA expression following preterm delivery (PTD) was 4.8 and 3.8 times (P<0.05), respectively, those following elective Caesarean section prior to labour at term (CST) and following vaginal delivery after spontaneous labour at term (SLT). The concentration of ICAM-1 protein in the PTD samples was 2.2 and 3.0 times (P<0.05) those in CST and SLT samples, respectively. The differences between the term groups were not significant. The results were substantially the same when a preterm spontaneous labour (PTL) subgroup, exclusive of deliveries complicated by pre-eclampsia or intrauterine growth restriction, was compared with the term groups. Choriodecidual ICAM-1 mRNA expression, but not ICAM-1 protein concentration, significantly correlated to the degree of leukocyte infiltration of the PTD gestational membranes. Neither correlated significantly to clinical indications of intrauterine or neonatal infection. These findings indicate that ICAM-1 is expressed by the human choriodecidua and that this expression is elevated with preterm labour and delivery, particularly with increased leukocyte infiltration.     

Conjugated linoleic acid induces mast cell recruitment during mouse mammary gland stromal remodeling

Conjugated linoleic acid (CLA) is a dietary chemopreventive agent that induces apoptosis in the mammary adipose vascular endothelium and decreases mammary brown adipose tissue (BAT) and white adipose tissue (WAT). To determine onset and extent of stromal remodeling, we fed CD2F1/Cr mice diets supplemented with 1 or 2 g/100 g mixed CLA isomers for 1-7 wk. BAT loss, collagen deposition, and leukocyte recruitment occurred in the mouse mammary fat pad, coincident with an increase in parenchymal-associated mast cells in mice fed both levels of CLA. Feeding experiments with purified isomers (0.5 g/100 g diet) demonstrated that these changes were induced by trans-10, cis-12 CLA (10,12-CLA), but not by cis-9, trans-11 CLA (9,11-CLA). This stromal remodeling did not require tumor necrosis factor (TNF)-alpha, a major cytokine in mast cells, as TNF-alpha null mice demonstrated collagen deposition, increased leukocytes, and BAT loss in the mammary fat pad in response to 10,12-CLA. To test the hypothesis that mast cells recruited in response to 10,12-CLA were required for stromal remodeling, Steel mice (WBB6F1/J-kit(W)/kit(W-V)), which lack functional mast cells, were examined for their stromal response to 10,12-CLA. Both wild-type and Steel mice showed a significantly increased leukocytic adipose infiltrate, collagen deposition, and decreased adipocyte size, although BAT was maintained in Steel mice. These results demonstrate that 10,12-CLA induces an inflammatory and fibrotic phenotype in the mouse mammary gland stroma that is independent of TNF-alpha or mast cells and suggest caution in the use of 10,12-CLA for breast cancer chemoprevention.     

Resveratrol blunts tumor necrosis factor-��-induced monocyte adhesion and transmigration

The leukocyte recruitment and transmigration across the endothelial barrier into the vessel wall are crucial steps in atherosclerosis. Leukocyte trafficking on the endothelium is elicited by induction of endothelial adhesion molecules, and its transmigration is mediated by degradation of basement membrane proteins through enzymatic activity of matrix metalloproteinases (MMP). The current study investigated whether resveratrol, a polyphenol present in grapes and red wine, was capable of inhibiting leukocyte adhesion to tumor necrosis factor (TNF)-α-activated endothelium. It was found that resveratrol inhibited the TNF-α-activated endothelial expression of vascular cell adhesion molecule-1 in a dose-dependent manner. In addition, resveratrol hampered THP-1 monocyte adhesion to activated endothelial cells. This study further examined whether resveratrol interfered with transendothelial migration of leukocytes. The MMP-2 gelatinolytic activity of endothelial cells was enhanced by TNF-α, which was attenuated by an addition of ≥25 µM resveratrol. In addition, 25 µM resveratrol mitigated the MMP-9 activity of THP-1 cells, followed by a marked inhibition of transendothelial migration. These results demonstrated that resveratrol suppressed monocyte adhesion and migration induced by TNF-α through modulating expression of adhesion molecules and gelatinolytic activity of MMP. These findings suggest that dietary resveratrol may be therapeutic agent for inhibiting leukocyte recruitment into the subendothelium during inflammatory atherosclerosis.     

Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3T3-L1 cells and C57BL/6J and ob/ob mice

Inflammation plays a major role in the development of chronic diseases such as cardiovascular disease and Type 2 diabetes. Further, it was demonstrated that obese animals and humans have significantly higher levels of circulating proinflammatory cytokines, such as interleukin-6 (IL-6). The aim of this study was to determine whether adipose tissue could be a major source of circulating IL-6 in leptin-deficient obese (ob/ob) mice by comparing the expression of IL-6 in different tissues of ob/ob mice. Our secondary goal was to determine whether preadipocytes are the source of adipose tissue IL-6. The ob/ob mice had higher levels of plasma IL-6 (P < 0.05) and adipose tissue IL-6 mRNA (P < 0.05) compared with lean mice. Interestingly, IL-6 mRNA levels of liver and spleen were not different between ob/ob and lean mice, whereas adipose tissue IL-6 mRNA levels were higher in the ob/ob mice compared with lean mice (P < 0.05). In addition, we showed that IL-6 secretion from the adipose tissue stromal vascular fraction cells was higher than that from fully differentiated adipocytes (P < 0.001). We further demonstrated that 3T3-L1 preadipocytes had significantly higher levels of lipopolysaccharide (LPS)-stimulated IL-6 mRNA and IL-6 secretion than differentiated 3T3-L1 adipocytes. Taken together, these data suggest that adipose tissue and preadipocytes from the adipose tissue stromal vascular fraction may contribute significantly to the increased plasma IL-6 levels in ob/ob mice.     

细胞间黏附分子-1与妊娠期高血压疾病发病的关系

目的:探讨ICAM-1与妊娠期高血压疾病发病的关系。方法:采用ELISA法检测妊娠期高血压疾病患者以及正常妊娠妇女血清中可溶性细胞间黏附分子(sICAM-1)的水平;SP法对胎盘组织进行免疫组化,分析ICAM-1的定位、分布和表达量。结果:①妊娠期高血压疾病组血清sICAM-1的水平为4.612 pg/ml,正常妊娠组为3.766 pg/ml,两组比较差异有统计学意义(P<0.001);妊娠期高血压疾病组内比较,差异均有统计学意义(P<0.05)。②妊娠期高血压疾病组胎盘ICAM-1的阳性表达率明显高于正常妊娠组(P<0.001);妊娠期高血压疾病组内比较,差异均有统计学意义(P<0.05)。③妊娠期高血压疾病组胎盘组织中ICAM-1的平均光密度值(MOD)为0.298 4,正常妊娠组为0.190 1,两组比较差异有统计学意义(P<0.001);妊娠期高血压疾病组内比较,差异均有统计学意义(P<0.05)。④妊娠期高血压疾病患者血清中sICAM-1水平以及胎盘中ICAM-1的平均光密度均升高,两者均随妊娠期高血压疾病病情的加重而升高,且两者之间呈正相关。结论:妊娠晚期血清sICAM-1的升高和胎盘组织中ICAM-1的表达增强可能是妊娠期高血压疾病的发病原因之一。     

香烟烟对血管内皮表达细胞间粘附分子-1的影响

目的探讨香烟烟对人血管内皮表达细胞间粘附分子-1的影响。方法以香烟烟为抗原刺激巨噬细胞株细胞,再用其上清液刺激人脐带静脉内皮细胞。采用ELISA法分别测定了经抗原刺激后3h、6h、12h、24h的巨噬细胞上清液中的肿瘤坏死因子-α(TNF-α);采用同样方法分析用抗原刺激巨噬细胞株细胞的上清处理血管内皮细胞3h、6h、9h、12h、24h培养基中可溶性细胞间粘附分子-1(sICAM-1)。结果随着处理时间的延长,TNF-α的表达量增多,实验组(4.967±0.802)pg/ml较对照组(3.181±0.214)pg/ml含量明显增加。统计结果提示,随孵育时间延长,sICAM-1表达的量增加,并且观察组(均数为0.0684ng/ml)比对照组(均数0.0459ng/ml)增加49%。结论香烟烟可以刺激人体最主要的抗原递呈细胞-巨噬细胞表达TNF-α,进一步使血管内皮细胞表达ICAM-1增加。     

Short-chain fatty acids modulate gene expression for vascular endothelial cell adhesion molecules

OBJECTIVE: Leukocyte infiltration into the intestinal wall is central to the pathogenesis of tissue injury that occurs in patients with a variety of inflammatory bowel diseases. Migration of leukocytes from the intestinal circulation into bowel tissues is mediated by chemotactic substances and adhesion molecules (i.e., intercellular adhesion molecule-1 [ICAM-1] and E-selectin) on the surface of endothelial cells lining blood vessels. Short-chain fatty acids (SCFAs) derived from dietary fiber decrease inflammatory responses in colon cells. However, the effect of SCFAs on vascular adhesion molecules is unknown. We investigated the effects of SCFAs on vascular endothelial cell adhesion molecule expression. METHODS: We assessed the effect of physiologically relevant concentrations of butyrate on expression of ICAM-1 protein and mRNA in cultures of human umbilical vein endothelial cells. We also assessed the effect of butyrate on levels of HLA-DR, E-selectin, vascular cell adhesion molecule-1, and endoglin. In additional experiments, we evaluated the effect of butyrate on ICAM-1 mRNA stability and the effect of valerate, isobutyrate, and propionate on ICAM-1 expression. The effect of butyrate on ICAM-1 expression was compared with that of trichostatin A, a specific inhibitor of histone deacetylase. Data were evaluated with Student's t tests or Tukey's multiple comparison tests, with P < 0.05 considered statistically significant. RESULTS: Butyrate concentrations of 2.5 to 5 mM significantly increased endothelial expressions of ICAM-1 protein and mRNA. The effect of butyrate (5 mM) on ICAM-1 expression was time dependent, with significant increases in levels occurring after 16 h of incubation. Butyrate (5 mM) also increased expression of E-selectin but not of HLA-DR, vascular cell adhesion molecule-1, or endoglin. Isobutyrate had little effect on ICAM-1 expression, whereas valerate and propionate significantly increased expression of ICAM-1 but were weaker stimulants compared with butyrate. Butyrate (5 mM) did not alter stability of ICAM-1 mRNA. The effect of butyrate (5 mM) was comparable to that of trichostatin A. The stimulatory effect of butyrate on ICAM-1 expression was reversed after 48 h of butyrate withdrawal. CONCLUSIONS: Butyrate increases vascular endothelial expressions of ICAM-1 and E-selectin. We speculate that butyrate-induced effects on vascular adhesion molecules modulate gut inflammation. The role of SCFAs and fiber in the pathogenesis and modulation of gut inflammation in vivo requires further study.     

N-乙酰半胱氨酸对缺氧缺血新生大鼠脑细胞间黏附分子-1及细胞凋亡的影响

目的探讨N-乙酰半胱氨酸(NAC)对缺氧缺血脑损伤(HIBD)大鼠脑细胞间黏附分子-1及细胞凋亡的影响。方法7d龄SD大鼠，90只，随机分成3组，(1)假手术组(Sham)(n=30)；(2)HIBD模型组(Control)(n=30)：HIBD模型后即刻腹腔注射等量生理盐水；(3)HIBD药物组(NAC)(n=30)：HIBD模型后即刻腹腔注射N-乙酰半胱氨酸(NAC)，200mg/kg。各组大鼠于处置后6h、12h、24h、48h、7d分别采用免疫组化法和Tunel法检测脑组织中细胞间黏附分子-1(ICAM—1)和细胞凋亡数目。结果HIBD模型组脑组织中ICAM—1的表达和细胞凋亡数与假手术组和HIBD药物组相比均升高，有显著性差异。结论NAC可抑制HIBD脑细胞ICAM-1的表达及脑细胞的细胞凋亡程度，NAC对缺氧缺血新生大鼠脑损伤有保护作用。     

Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue

ABSTRACT: BACKGROUND: Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue. METHODS: Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject. RESULTS: Gene expression levels of sphingomyelinases, enzymes that hydrolyze sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot. CONCLUSIONS: Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue.     

Accelerated Mammary Tumor Onset in a HER2/Neu Mouse Model Exposed to DDT Metabolites Locally Delivered to the Mammary Gland

Background: The association of DDT (dichlorodiphenyltrichloroethane) with breast cancer is controversial, but animal studies directly linking DDT to risk are lacking. Concerns with DDT reside in its environmental persistence, bioaccumulation in breast adipose tissue, and endocrine-disrupting actions. Whereas most attention has been focused on estrogenic congeners, we tested the cancer-inducing potential of the antiandrogen, p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the most prevalent and persistent DDT metabolite.Objectives: We aimed to determine whether developmental exposure to p,p′-DDE stored in adipose tissue surrounding the cancer-prone mammary epithelium of MMTV-Neu mice influences tumor development.Methods: For localized delivery, Elvax 40P pellets containing p,p′-DDE were implanted into the mammary fat pads of prepubertal female mice. We compared mammary tumor development with p,p′-DDE with development in response to its estrogenic isomer, o,p′-DDE [1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethylene], and a mixture of both isomers.Results: p,p′-DDE implants significantly accelerated mammary tumor onset compared with vehicle Elvax implants. o,p′-DDE had similar results, but only at ≤ 10 months of age. Lipid-adjusted levels of p,p′-DDE in mammary adipose tissue and serum in young mice were within the ranges of human exposure, whereas concentrations in aged mice were low to undetectable. Exposure to a 2:1 ratio of p,p′-DDE:o,p′-DDE did not result in the younger latency observed with the individual isomers.Conclusions: p,p′-DDE exposure at concentrations relevant to human exposure accelerates mammary carcinogenesis in mice, possibly through hormonal and/or other actions. These data suggest that DDE exposure would promote, but not cause, mammary tumorigenesis. Developmental exposure in immature mammary tissue continues to affect tumor onset even after p,p′-DDE levels have declined. Future studies are needed to determine whether early exposure to p,p′-DDE correspondingly predisposes women to early-onset breast cancer.     

新生大鼠缺氧缺血脑损伤细胞间粘附分子-1及细胞凋亡变化的关系

[目的]研究新生大鼠缺氧缺血脑损伤(hypoxicischemicbraindamage,HIBD)后脑细胞间粘附分子-1及细胞凋亡的变化及其相互关系,为临床HIBD的诊治提供理论依据。[方法]7日龄SD大鼠60只,随机分成两组:正常对照组30只,HI组(hypoxic-ischemic,HI)30只:HIBD)造模。大鼠于处置后6、12、24、48h、7d:分别采用免疫组化法和Tunel法检测脑组织中细胞间粘附分子-1(intercellularadhesionmoleculel-1,ICAM-1)的表达和细胞凋亡数目。[结果]与正常对照组相比,HI组脑组织中ICAM-1的:表达和细胞凋亡数在术后12h升高,差异有非常显著性(P<0.01),24h和48h达高峰。ICAM-1和细胞凋亡之间相关系数r=0.829,P<0.01。[结论]新生大鼠缺氧缺血脑损伤后脑细胞ICAM-1的表达和细胞凋亡均增加,两者间呈高度线性正相关关系。     

Soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 concentrations, and leukocyte count in smokers

The leukocyte count and concentrations of_sICAM-1 and_sVCAM-1 in smokers were investigated. The subjects were 96 persons (31 smokers and 65 nonsmokers) hospitalized for a complete health checkup examination. There were no differences between the two groups for background factors (age (nonsmokers, 56.2 ± 9.2 vs smokers, 52.6 ± 11.3)gender ratio (m/f)(nonsmokers, 47/18 vs smokers, 24/7) and drinker ratio (+/-) (nonsmokers, 45/20 vs smokers, 26/5)). For smokers, the average number of cigarettes smoked daily, smoking period(ys) and Brinkman Index were 21.4 ± 10.4, 26.2± 14.5 and 584.2 ± 476.9, respectively. In smokers, total leukocyte count (l μ 1) (6371.0 ± 1303.4 vs 5063.1 ± 1279.1,_p<0.0001), and_sICAM-1 concentration (ng/ml) (202.6 ± 64.0 vs 163.0 ± 60.8,_p<0.01) were higher than those in nonsmokers. No significant difference in the_sVCAM-1 concentration was shown between the two groups. Items showing large correlation coefficients with the number of cigarettes smoked daily were the total leukocyte count (r = 0.45,_p<0.0001) and_sICAM-1 (r = 0.36,_p<0.0001). In smokers,_sICAM-1 showed correlation with the total leukocyte count (r = 0.42,_p<0.05) . We conclude diat the leukocyte count and_sICAM-1 concentration in healthy smokers are higher than those in nonsmokers.     

Effects of irbesartan on the growth and differentiation of adipocytes in obese zucker rats

OBJECTIVE: The aim of this study was to evaluate the effects of the selective angiotensin receptor 1 antagonist irbesartan on the growth and differentiation of the adipocytes in obese Zucker fa/fa rats. RESEARCH METHODS AND PROCEDURES: Obese Zucker fa/fa rats were treated by oral route for 3 weeks with irbesartan at doses of 3-10-30 mg/kg per day. The adipocyte differentiation was evaluated by analyzing tissue samples of white (retroperitoneal) or brown (interscapular) adipose tissue for the presence of peroxisome proliferator activated receptor gamma, leptin, and the activity of glycerol-3-phosphate dehydrogenase. RESULTS: This study showed that the treatment of obese Zucker fa/fa with irbesartan effectively reduced the differentiation of adipocytes within brown (interscapular) and white (retroperitoneal) adipose tissue. In fact, irbesartan significantly (p < 0.01) and dose-dependently reduced the tissue levels of leptin, peroxisome proliferator activated receptor gamma, and the activity of the enzyme glycerol-3-phoshate dehydrogenase accepted markers of adipocyte differentiation. None of the tested doses of irbesartan affected these markers in non-obese rats. DISCUSSION: The antagonism of the angiotensin receptor 1 receptors with irbesartan reduces the adipogenic activity of angiotensin II in obese Zucker rats, with the endpoint being reduction of the growth and differentiation of the adipocytes within the adipose tissue.     

细胞间黏附分子-1在早产胎膜早破患者胎膜组织中的表达及意义

目的:研究细胞间黏附分子-1(ICAM-1)在早产胎膜早破患者胎膜组织中的表达及意义。方法:收集产科已确诊的早产胎膜早破的38例患者的胎膜为研究组,收集与研究组孕妇孕周相对应的胎膜完整的自发早产的36例孕妇的胎膜为对照组,应用免疫组化二步法检测两组胎膜ICAM-1的表达,并进行临床病理的相关性分析。结果:两组胎膜中均存在不同程度的ICAM-1阳性表达,两组比较差异有统计学意义(P<0.05);研究组中有21例(55.26%)存在绒毛膜羊膜炎,对照组中有13例(36.11%)存在绒毛膜羊膜炎,两组比较差异有统计学意义(P<0.05),研究组ICAM-1的表达与绒毛膜羊膜炎的相关系数为0.90,对照组ICAM-1的表达与绒毛膜羊膜炎的相关系数为0.72,且病理显示炎症越重的胎膜,其ICAM-1的阳性表达越明显。结论:ICAM-1的表达与胎膜的感染程度相关,感染越重的胎膜其ICAM-1的表达越明显,提示妊娠的结局相对严重;ICAM-1在早产早破胎膜中的表达也提示其在早产胎膜早破的发病过程中可能起一定的作用。     

Enteral feeding preserves gut Th-2 cytokines despite mucosal cellular adhesion molecule-1 blockade

BACKGROUND: Parenteral nutrition (PN) decreases gut-associated lymphoid tissue (GALT), the intestinal IgA stimulating cytokines IL-4 and IL-10 in gut homogenates, intestinal IgA levels and the expression of Peyer patch (PP) mucosal cellular adhesion molecule-1 (MAdCAM-1), an adhesion molecule found on the high endothelial venules of PP and other tissues. IL-4 in PP stimulates MAdCAM expression in vitro. MAdCAM-1 blockade with MECA-367 reduces GALT cell populations to PN levels but maintains intestinal IgA levels if the animals are chow fed. This study compares IL-4 levels in PP of chow and PN fed mice and measures the effects of MAdCAM blockade on IL-4 and IL-10 levels in gut homogenates of chow fed mice. We hypothesized that in vivo IL-4 levels drop in PP of PN fed mice and IL-4 and IL-10 levels are maintained after MAdCAM-1 blockade in chow fed mice. METHODS: Exp 1: 18 mice received chow or PN for 5 days to determine PP IL-4 levels. Exp 2: 44 mice were randomized to chow + control monoclonal antibody (mAb), chow + MECA-367 (anti-MAdCAM-1 mAb) or PN for 4 days before measurement of IL-4 and IL-10 levels in gut homogenates. RESULTS: Exp 1: IL-4 levels in vivo were lower in PP of PN-fed mice than chow fed mice (92.0 +/- 15.1 pg/mL vs 251.1 +/- 14.8, p = .0003). Exp 2: IL-4 levels were significantly higher in chow + control mAb (187.1 +/- 44.1 pg/mL) and chow + MECA-367 (110.9 +/- 19.1 pg/mL) groups than PN mice (21.8 +/- 30.6 pg/mL, p < .02 vs chow + control or chow + MECA-367). IL-10 levels were significantly lower with PN (23.1 +/- 40.9 pg/mL) with chow+control (174.0 +/- 22.2 pg/mL p < .01), or chow + MECA-367 (181.7 +/- 23.1 pg/mL, p < .02 vs PN). CONCLUSIONS: PN-feeding reduces in vivo IL-4 levels in PP (consistent with lowered MAdCAM-1 expression) and IL-4 and IL-10 levels in gut homogenates compared with chow. Despite MAdCAM-1 blockade, enteral feeding preserved gut IL-4 levels and increased IL-10 levels consistent with preserved IgA levels.     

Protective effects of taurine on endothelial cells impaired by high glucose and oxidized low density lipoproteins

BACKGROUND: Endothelial dysfunction, common to diabetes and cardiovascular diseases, is an early step in the development of atherosclerosis and diabetic angiopathies. Deficiencies of taurine have been related to diabetes and cardiovascular diseases. AIMS OF THE STUDY: We investigated whether taurine provides protective action against endothelial dysfunction induced by hyperglycemia and/or oxidized low density lipoproteins (oxLDL). METHODS: Quiescent human umbilical cord venous endothelial cells were exposed for 20 h to high glucose (35 mM) and/or oxLDL (60 microg/ml) alone and in presence of taurine (0.5-2.5 mg/ml). Apoptosis, caspase-3 activity, soluble(s) and cell surface expressions of vascular cellular (VCAM-1) and intercellular (ICAM-1) adhesion molecules were determined. Results are given as a percentage of the low glucose medium control. Apoptosis, VCAM-1 and ICAM-1 expressions were related to cell number. RESULTS: Hyperglycemia increased apoptosis to 162.5 +/- 19.2%, caspase-3 activity to 153.2 +/- 10.3%, cell-surface expression of VCAM-1 to 125.1 +/- 5.8%, the expression of ICAM-1 to 123.7 +/- 2.8% and sICAM-1 to 146.5 +/- 7.9%. Taurine (0.5-2.5 mg/ml) restored apoptosis, caspase-3 activity and expressions of VCAM-1 and ICAM-1. OxLDL (60 microg/ml) increased apoptosis to 114.8 +/- 3.1%; taurine (2.5 mg/ml) reduced this apoptosis to 40.5 +/- 4.1%. The combination of hyperglycemia and oxLDL increased apoptosis to 211.7 +/- 11.6%. This increase was normalized by taurine (2.5 mg/ml) to 97.9 +/- 12.8%. CONCLUSION: Taurine protects HUVECs from endothelial dysfunction induced by hyperglycemia through down-regulation of apoptosis and adhesion molecules. Counteracting the combination of oxLDL and hyperglycemia requires pharmacological concentrations of taurine.