Labour-associated expression of intercellular adhesion molecule-1 (ICAM-1) in placental endothelial cells indicates participation of immunological processes in parturition.

Inflammatory cytokines induce or upregulate de novo expression of cell adhesion molecules on endothelial and epithelial cells. In order to demonstrate inflammatory reactions within placental tissues in association with normal term as well as non-infection-induced preterm labour, the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) was examined by immunohistochemical methods in both trophoblastic villi (n=123) and umbilical cord (n=61). As a result, ICAM-1 immunoreactivity was exclusively localized in the endothelial cells of the fetal vascular system, while VCAM-1 and ELAM-1 were not detected. Whereas ICAM-1 was not expressed in early pregnancy (9-12 weeks of gestation), it could be weakly detected at the end of pregnancy in cases of elective caesarean delivery in the absence of labour, and was significantly more strongly expressed in cases of vaginal delivery after spontaneous onset of normal term labour. Significantly increased immunoreactivity of ICAM-1 within umbilical cord tissues was also found in association with uncontrollable preterm labour in the absence of intrauterine infection which was excluded after histological examination of fetal membranes, umbilical cord and chorionic plate. We conclude that ICAM-1 expression in the endothelium of the fetal vascular system is associated with the presence of labour and reflects participation of immune-inflammatory reactions in labour-promoting mechanisms.     

The fetomaternal interface shows vascular hypoglycosylation in the tammar wallaby Macropus eugenii: Comparison with a range of non-mammalian and eutherian placentae

Introduction

Blood vessel glycosylation at the fetomaternal interface of four near-term specimens of tammar wallaby, Macropus eugenii, has been examined at days 23–26 of the 26.5 day pregnancy and compared with that of other species.

Methods

A panel of 23 lectins was used to compare vasculature in tammar with non-mammalian (shark, skink) and eutherian species at early and late gestation (camel, horse and alpaca), and term/near-term (cat, lion, dog, mink and elephant).

Results

Strikingly low levels of all the glycans tested, apart from sialic acids, were found in capillary endothelium of both the trilaminar omphalopleure and underlying surface endometrium of the tammar, though deeper endometrial vessels showed normally high levels of glycosylation. Only maternal vasculature of the mink placenta showed a comparable lack of expression.

Discussion

One reason for a reduced endothelial glycocalyx may be to facilitate diffusion of gases and nutrients as the tammar trophoblast lacks the indentation by overlying vessels that is seen in the other near-term placentae. Early epitheliochorial placentae of other species with equal diffusion distances to the tammar, showed normal vascular glycosylation. However, their pregnancies are much longer.

Conclusion

The hypoglycosylation of tammar vessels at the fetomaternal interface may allow continued transfer of nutrients and gaseous exchange during the extremely rapid period of organogenesis which occurs during the short 26.5 day pregnancy of this marsupial. Given the short gestation period of the tammar, we suggest that a thinner endothelial glycocalyx has evolved to facilitate diffusion of gases and nutrients between the maternal and fetal compartments.     

Systemic inflammation, cellular influx and up-regulation of ovarian VCAM-1 expression in a mouse model of polycystic ovary syndrome (PCOS)

PCOS, a major cause of anovulatory sterility, is associated with obesity, insulin resistance and chronic inflammation. New evidence suggests that the immune system aggravates the clinical features of PCOS. Our aim was to study the immune, metabolic and endocrine features of a mouse model of PCOS elicited by androgenisation using dehydroepiandrosterone (DHEA). We observed a significant weight gain and insulin resistance in DHEA-androgenised mice, coupled with the formation of ovarian follicular cysts. DHEA up-regulated the expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the granulosa cell layer of the majority of cysts, and VCAM-1 expression in the theca cell layer of all follicles and cysts. The expression of these markers was low in control tissue. Peritoneal cells from PCOS-mice showed enhanced production of inflammatory cytokines, suggesting an association between chronic inflammation and PCOS. In addition, DHEA-androgenisation induced the activation of CD4(+) cells both in vivo and in vitro, and their expression of the respective ligands for VCAM-1 and ICAM-1, VLA-4 and LFA-1, as assessed in vitro. CD4(+) cells were present in androgenised ovaries, especially in the granulosa cell layer of cysts with high VCAM-1 expression. Herein, we present novel evidence that the immune system is activated systemically and locally in a mouse model for PCOS. We propose that VCAM-1 is involved in aggravating PCOS symptoms by promoting leukocyte recruitment to the ovaries and perpetuating local inflammation. These findings offer novel therapeutic opportunities for PCOS, such as blockage of VCAM-1 expression.     

干预CD86协同刺激信号在诱导母胎界面Th2型免疫偏倚中的作用

目的 :探讨干预CD86协同刺激信号在诱导母胎界面局部形成Th2型免疫偏倚中的作用。方法 :将正常妊娠模型 (CBA×BALB/c)和自然流产模型 (CBA×DBA/ 2 )CBA孕鼠均分为两组 ,于孕第 4、6、8天 ,对照组腹腔注射大鼠IgG ,实验组腹腔注射大鼠抗小鼠CD86mAb ;孕第 9天 ,ELISA测定母胎界面组织培养上清中Th1型 (IFN γ、TNF α) /Th2型(IL 4、IL 10 )细胞因子表达水平 ,并计算IL 4 /IFN γ、IL 10 /IFN γ比值 ;孕第 12天比较两种模型各组的胚胎吸收率。结果 :正常妊娠模型中 ,干预CD86协同刺激信号对母胎界面原有的Th2型免疫偏离及妊娠预后均无显著影响。自然流产模型中 ,干预CD86协同刺激信号能够诱导母胎界面局部形成Th2型免疫偏倚并显著改善其妊娠预后。结论 :于孕早期 ,干预CD86协同刺激信号能够改善母胎界面局部细胞因子微环境 ,形成维持正常妊娠所需的Th2型免疫偏倚 ,诱导母胎免疫耐受     

Systemic inflammation,cellular influx and up-regulation of ovarian VCAM-1 expression in a mouse model of polycystic ovary syndrome (PCOS)

PCOS, a major cause of anovulatory sterility, is associated with obesity, insulin resistance and chronic inflammation. New evidence suggests that the immune system aggravates the clinical features of PCOS. Our aim was to study the immune, metabolic and endocrine features of a mouse model of PCOS elicited by androgenisation using dehydroepiandrosterone (DHEA). We observed a significant weight gain and insulin resistance in DHEA-androgenised mice, coupled with the formation of ovarian follicular cysts. DHEA up-regulated the expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the granulosa cell layer of the majority of cysts, and VCAM-1 expression in the theca cell layer of all follicles and cysts. The expression of these markers was low in control tissue. Peritoneal cells from PCOS-mice showed enhanced production of inflammatory cytokines, suggesting an association between chronic inflammation and PCOS. In addition, DHEA-androgenisation induced the activation of CD4⁺ cells both in vivo and in vitro, and their expression of the respective ligands for VCAM-1 and ICAM-1, VLA-4 and LFA-1, as assessed in vitro. CD4⁺ cells were present in androgenised ovaries, especially in the granulosa cell layer of cysts with high VCAM-1 expression. Herein, we present novel evidence that the immune system is activated systemically and locally in a mouse model for PCOS. We propose that VCAM-1 is involved in aggravating PCOS symptoms by promoting leukocyte recruitment to the ovaries and perpetuating local inflammation. These findings offer novel therapeutic opportunities for PCOS, such as blockage of VCAM-1 expression.     

粘附分子在妊高征脐血管表达的探讨

目的 :观察粘附分子在妊娠高血压综合征 (妊高征 )脐血管内皮细胞上的表达 ,探讨它在妊高征血管内皮细胞损伤过程中的作用。方法 :用免疫组化染色法 (SP法 )检测 4 5例妊高征脐血管 (妊高征组 )和 30例正常妊娠脐血管 (对照组 )上E -选择素、血管细胞粘附分子 (VCAM - 1)、细胞间粘附分子 - 1(ICAM - 1)、血小板 /内皮细胞粘附分子(PECAM - 1)的表达。结果 :E -选择素在中、重度妊高征组脐血管内皮细胞上的表达明显高于轻度妊高征组和对照组 (P <0 .0 5 )。ICAM - 1和PECAM - 1在妊高征组和对照组脐血管内皮细胞上的表达差异无显著性 (P >0 .0 5 )。VCAM - 1在妊高征组和对照组脐血管内皮细胞上均几乎无表达。结论 :E -选择素介导白细胞等免疫细胞与内皮细胞粘附 ,在血管内皮细胞损伤过程中起作用     

淋巴细胞免疫治疗对小鼠自然流产模型母胎界面CD80~+表达及妊娠结局的影响

目的:评价CBA/J×DBA/2小鼠配对组合作为反复自然流产模型的生殖力特点,及其与母胎交界CD80表达间的关系,并研究淋巴细胞免疫治疗(lymphocyte immunotherapy,LIT)对CD80表达水平的影响。方法:对CBA/J×DBA/2小鼠的生殖力特点进行为期120d的观察,并与生殖力正常的4种对照组进行比较。另计算15对CBA/J×DBA/2小鼠孕13d的胚胎吸收率,并用CD80-FITC和CD45-PE双色流式细胞术检测CD80细胞在母胎交界面的构成比。为了明确CD80~+细胞的身份,检测了CD3、DX5(NK细胞)和MHC-Ⅱ在CD80细胞群中的表达水平。此外,检测LIT组与未治疗组CBA/J×DBA/2小鼠胚胎吸收率和CD80细胞的阳性率。结果:CBA/J×DBA/2小鼠的流产特点是为孕10d左右的反复流产。CBA/J×DBA/2小鼠孕13d的胚胎吸收率显著高于BALB/c×DBA/2小鼠(30.8％±16.6％vs.7.7％±6.7％,P相似文献   

Fetomaternal transfusion and pregnancy outcome after cordocentesis

OBJECTIVE: To study the extent of fetomaternal transfusion and the outcome of pregnancy after cordocentesis. MATERIAL AND METHODS: 268 women underwent percutaneous fetal umbilical cord blood sampling for fetal karyotyping between 15 and 26 gestations of weeks. Complete follow-up was available in 221 (82.5%) of the cases. Cordocentesis was performed under continuous real-time ultrasound guidance. The duration of the procedure and the post-procedural bleeding time was counted in seconds. Fetomaternal transfusion was calculated by using the measurements of the maternal serum levels of alpha-fetoprotein before and after the procedure. The data were analyzed by Student's t and multiple regression tests. RESULTS: The maximum and mean amounts of fetomaternal transfusion were 1.067 and 0.061 ml, respectively. Twenty percent or more alpha-fetoprotein elevation was in 35.4% of the cases. Positive correlation was found between bleeding time after cordocentesis and fetomaternal transfusion (r = 0.174, p < 0.0129) as well as between the duration of the procedure (r = 0.165, p < 0.0171) and the amount of fetomaternal transfusion. Comparing the cordocentesis at the placental insertion site and at the free cord loop, a smaller amount of fetomaternal transfusion was observed (p < 0.0123) in the latter. Transplacental passage was associated with a higher amount of fetomaternal transfusion (p < 0.0067). No association was found between the extent of fetomaternal transfusion and the outcome of pregnancy. The fetal loss related to the cordocentesis was 0.50%. CONCLUSIONS: The extent of fetomaternal transfusion was influenced by the subsequent four parameters: procedural time, bleeding time, puncture site and transplacental penetration. The lack of the association between the degree of fetomaternal transfusion and the outcome of pregnancy, along with the low (0.50%) post-procedural fetal loss rate, suggest that cordocentesis is clinically a safe procedure.     

Vascular addressins in the uterus and pancreas of type 1 diabetic mice in early pregnancy

Distinctive patterns of vascular cell adhesion molecule expression in early mouse decidua establish niches that recruit different subtypes of immune cells. In normal gestation day (gd)8 decidua, vascular cell adhesion molecule (VCAM)-1 and mucosal addressin cell adhesion molecule (MAdCAM)-1 occur in different regions enriched by uterine Natural Killer (uNK) cells and monocytes, respectively. UNK cells prepare endometrial spiral arteries for pregnancy-induced structural modifications, a process deficient in decidua of type 1 diabetic mice and women. In non-obese diabetic (NOD) mice, onset of insulitis coincides with islet expression of VCAM-1, MAdCAM-1 and peripheral lymph node addressin (PNAd), a molecule implicated in extravasation of human uNK precursor cells. We used immunohistochemistry to address the combined effects of diabetes and pregnancy on gd6 and 8 pancreatic and decidual expression of VCAM-1, MAdCAM-1 and PNAd and assessed the effect of diabetes on early uNK cell numbers. Normoglycemic (n) and diabetic (d) NOD and C57Bl/6 (B6) mice were studied. Pregnancy increased addressin expression in the pancreata of all mice with n- and d-NOD pancreata having stronger endothelial expression of VCAM-1, MAdCAM-1 and PNAd than B6. VCAM-1 expression was localized to uterine endothelium, including that of spiral arteries and was lower in d- than in n-NOD or B6 mice. MAdCAM-1 was localized to uterine endothelium and was lower in n- and d-NOD than in B6. PNAd expression was only observed in uterine epithelium and was stronger in d- than in n-NOD or B6. In all groups, only VCAM-1 had stronger expression in decidua than in pancreas. A mild elevation in uNK cells was present in n-and d-NOD mice at gd6 but not at gd8 when a higher proliferation index was found compared with B6. Thus, in type 1 diabetic gestations in mice, signals for the recruitment of circulating cells are reduced in uterus and elevated in pancreas.     

川芎嗪对妊娠高血压综合征患者脐静脉内皮细胞粘附分子表 …

目的 探讨妊娠高血压综合征（妊高征）患者血浆诱导培养的脐静脉内皮细胞（ＨＵＶＥＣ）表面细胞间粘附分子－１（ＩＣＡＭ－１）、血管细胞粘附分子－１（ＶＣＡＭ－１）的表达以及川芎嗪对其的影响。方法 采用胶原酶、胰蛋白酶混合灌注消化法,对正常妊娠妇女（正常妊娠组）、妊高征患者（妊高征组）的ＨＵＶＥＣ进行培养,待细胞融合成单层后,加或不加川芎嗪进行预处理,并以正常未妊娠妇女（对照组）作为对照。再加入上述３组     

川芎嗪对子痫前期脐血清诱导脐静脉内皮细胞NF-κB活性及VCAM-1表达的影响

目的:探讨川芎嗪对子痫前期患者脐静脉血清诱导脐静脉内皮细胞(HU-VEC)核因子-κB(NF-κB)活性及其靶基因血管细胞黏附分子-1(VCAM-1)表达变化的影响。方法:用胰酶消化法培养正常妊娠HUVEC,传代后待细胞长满至70%~80%,加或不加川芎嗪作用30min后分别加入正常妊娠及子痫前期脐静脉血清,培养48h后,MTT测定细胞活力,流式细胞学测定细胞凋亡率,Western-blot测定HUVEC NF-κB的表达,酶联免疫检测VCAM-1的表达。结果:子痫前期患者脐静脉血清培养HUVEC的增殖活力明显低于正常妊娠组,胞核NF-κB及VCAM-1表达明显高于正常妊娠组(P<0.01),子痫前期患者脐静脉血清培养HUVEC的细胞凋亡率明显高于正常妊娠组(P<0.01)。加川芎嗪预处理后,子痫前期组HUVEC增殖活力明显增加,细胞凋亡率、胞核NF-κB及VCAM-1表达明显下降(P<0.01)。结论:川芎嗪可抑制子痫前期患者脐静脉血清诱导的HU-VEC凋亡,NF-κB的核转位及VCAM-1的表达。     

Fetomaternal hemorrhage following trauma

Fetomaternal hemorrhage can result from different types of trauma and may be followed by fetal anemia, fetal death, or isoimmunization. We prospectively studied the frequency and volume of fetomaternal hemorrhage, fetal well-being, abruptio placentae, and fetal outcome in 32 pregnant patients suffering recent trauma. Fetomaternal hemorrhage occurred in nine of 32 trauma patients (28%) with a mean volume of 16 ml +/- 14.3(SD). There was a statistically significant difference in the frequency and mean volume of fetomaternal hemorrhage in this group over that in gestational-age-matched controls. Neither the nature of the trauma nor the gestational age was related to the frequency or volume of fetomaternal hemorrhage. The outcome in three of the nine trauma patients who sustained fetomaternal hemorrhage was poor; fetal anemia, paroxysmal atrial tachycardia, and fetal death occurred in each one. Maternal trauma remains a significant cause of maternal and fetal morbidity and death, and the use of the Kleihauer-Betke analysis is indicated to identify fetomaternal hemorrhage. Rh-immune globulin therapy should be given to Rh-negative patients with fetomaternal hemorrhage.     

2-Methoxyestradiol prevents monocyte adhesion to vascular endothelial cells via downregulation of VCAM-1 expression

2-Methoxyestradiol (2-ME) reduces atherosclerotic lesion formation. However, the underlying mechanisms remain largely unknown. In this work, we investigated the effect of 2-ME on monocyte adhesion to vascular endothelial cells. Lipopolysaccharides (LPS) greatly increased the attachment of monocyte onto cultured human umbilical vascular endothelial cells (HUVECs), which was inhibited by 2-ME in a dose- and time-dependent manner, or by the vascular cell adhesion protein-1 (VCAM-1) neutralizing antibody, suggesting that a functional releationship between 2-ME and VCAM-1 may exist. In accordance with this, treatment with 2-ME (10^?7–10^?5 M) for 6–48?h downregulated VCAM-1 protein expression. Meanwhile, the nuclear factor κB (NF-κB) p65 subunit activity and its nuclear translocation was inhibited by 2-ME in HUVECs. The PI3K inhibitor wortmannin or the specific Akt siRNA both inhibited the effects of 2-ME, suggesting that 2-ME inhibited p65 activity via PI3K/Akt signaling. In conclusion, 2-ME inhibits VCAM-1 expression and thus prevents monocyte adhesion to vascular endothelial cells via regulation of PI3K/Akt and NF-κB signaling. These findings will be helpful for better understanding the mechanisms through which 2-ME improves endothelial function.     

Increased maternal plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) in pregnancy induced hypertension (PIH)

One of the reason of PIH problems may be due to the presence of increased circulating levels of cell adhesion molecules, markers of endothelial damage and leukocyte activation. The objective was to evaluate the plasma levels of soluble vascular cell adhesion molecule in maternal peripheral blood of patients with PIH (pregnancy induced hypertension) and compared to those of normal healthy women with uncomplicated pregnancy. Maternal plasma samples were prepared from peripheral venous blood collected from 10 patients with PIH and 10 matched normotensive patients with uncomplicated pregnancies. Samples were assayed for soluble VCAM-1 by specific enzyme-linked immunosorbent assay (ELISA). Women with PIH had significantly higher plasma level of soluble VCAM-1 as compared with healthy pregnant women without PIH (653.50 vs. 456.39 ng/mL, respectively, p < 0.005). Our results on the increased plasma levels of soluble VCAM-1 in patients with PIH provide evidence for endothelial activation of PIH. It suggest that increased plasma level of soluble VCAM-1 could be an early marker of the maternal syndrome of PIH.     

Lack of proinflammatory effects of free fatty acids on human umbilical cord vein endothelial cells and leukocytes

AIM: To determine whether the free fatty acids (FFAs), oleic, linoleic, and palmitic acid, found elevated before 20 weeks of pregnancy in those women who later develop preeclampsia, induced changes in expression of the vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), or E-selectin in cultured human umbilical cord vein endothelial cells (HUVEC), and integrin subunit CD11b, L-selectin or intracellular reactive oxygen species (ROS) in leukocytes. METHODS: The VCAM-1, ICAM-1, and E-selectin expression were measured using ELISA in HUVEC after incubation with 100 micromol of either oleic, linoleic, or palmitic acid for 6 hr and 24 hr. The co-reactivity with lipopolysaccharide (LPS), the amount of VCAM-1 mRNA in the cells, and soluble VCAM-1 in the incubation medium were measured as well. Leukocyte adhesion molecules and ROS were measured after incubation with 750 microm of either of the FFAs in a whole blood model using flow cytometry. RESULTS: No effects of the FFAs tested were found on the HUVEC or leukocyte adhesion molecule expression or intracellular ROS. The only exception to this was palmitic acid incubation, which significantly lowered the VCAM-1 expression in HUVEC after 24-hr incubation and also slowed the decay of VCAM-1 expressed after stimulation with LPS. CONCLUSIONS: The lack of significant proinflammatory changes of the FFAs tested might indicate that the elevated plasma levels of FFAs seen in preeclampsia most probably are products of the preeclamptic process rather than a causative factor.     

泰山磐石散对复发性流产小鼠母胎界面Th1/Th2细胞因子及妊娠预后的影响

目的:观察泰山磐石散对复发性流产小鼠母胎界面Th1/Th2细胞因子及妊娠预后的影响,为泰山磐石散临床应用提供新的实验依据。方法:采用经典造模方式DBA/2小鼠与CBA/J杂交,获得复发性流产小鼠模型,随机将与DBA/2小鼠合笼的60只CBA/J妊娠小鼠分为模型组、中药低剂量组、中药中剂量组、中药高剂量组和阳性对照组;与BALB/C合笼的10只CBA/J孕鼠作为正常妊娠模型。于妊娠14 d后处死孕鼠,观察小鼠胎盘丢失情况,并提取培养胎界母细胞,24 h后收集细胞上清液,酶联免疫吸附测定(ELISA)法检测上清液中肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)、白细胞介素4(IL-4)和IL-10含量。结果:经泰山磐石散治疗后,与模型组比较,复发性流产小鼠胎盘丢失率明显改善,母胎界面细胞上清液中Th1型细胞因子IFN-γ明显降低,Th2型细胞因子IL-4、IL-10明显升高,Th1/Th2免疫调节失衡明显改善,以中药高剂量组改善最为明显。结论:泰山磐石散能改善复发性流产小鼠胎盘丢失情况,其具体机制可能是通过调节Th1/Th2免疫调节平衡实现。     

Intracellular adhesion molecule concentrations in women who smoke during pregnancy

OBJECTIVE: Smoking and endothelial dysfunction are associated with adverse pregnancy outcomes. The effect of smoking on vascular endothelium during pregnancy has not been well studied. Our objectives were to determine if smoking has an impact on endothelial function in pregnancy by comparing markers of endothelial function and to evaluate the contribution from different cellular sources. METHODS: We measured markers of endothelial function in a prospective cohort of 198 primiparous women who had 325 plasma samples obtained throughout pregnancy. Samples were assayed for intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin. Smoking status was determined by serum cotinine concentration. Analyses of adhesion molecules were performed for 4 gestational age intervals by using Mann-Whitney and Kruskal-Wallis tests. Gene expression for ICAM-1 was determined by real-time polymerase chain reaction from placental biopsies. A human umbilical vein endothelial cell (HUVEC) culture model was utilized to evaluate the effect of cotinine on endothelial cell production of ICAM-1. RESULTS: ICAM-1 is increased, VCAM-1 was not different, and E-selectin was decreased among smokers at various times during pregnancy. Placental production of ICAM-1 was decreased in women who smoked (P = .02) as measured by real-time polymerase chain reaction. Human umbilical vein endothelial cells production of ICAM-1 increased with heavy concentrations of cotinine exposure (P < .01). CONCLUSION: Smoking during pregnancy is associated with vascular perturbations, as evidenced by increased concentrations of serum ICAM-1. It appears unlikely that the source of the increased ICAM-1 is the placenta. The endothelium most likely contributes to increased maternal ICAM-1 in heavy smokers, but a leukocyte source cannot be ruled out. LEVEL OF EVIDENCE: II-2.