Expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of peripheral blood lymphocytes of pregnant women with pregnancy-induced hypertension

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1, CD54) is involved in process of leukocytes adhesion to endothelium as well as in their migration to surrounding tissues. There is much evidence that pregnancy-induced hypertension (PIH) presents a state of endothelial destruction mediated partially by increased ICAM-1 expression on endothelial cells and neutrofils. DESIGN: The aim of this study was to evaluate the expression of ICAM-1 (CD54) molecule on the peripheral blood lymphocytes of pregnant women with PIH studied "in vitro". MATERIALS AND METHODS: Preeclampsia (PE) and transient hypertension (TH) were defined according to USA National Health Institute criteria. The study group consisted of 16 women with preeclampsia (PE), 12 women with transient hypertension (TH) and 9 women with physiological pregnancy. The group of 8 nonpregnant women served as controls. Exclusion criteria were: uterine contractions, infection and steroid therapy before blood sampling. Peripheral blood was obtained by venipuncture. Lymphocytes were isolated and cultured by using standard procedures. Mitogenic doses of phytohaemaglutynin (PHA) were added to each culture. Immunofluorescent marking techniques with anty-CD54 one-step monoclonal antibodies were performed. Analysis was made with FACSCalibur flow-cytometer with 488 nm argon laser using CellQuest programme. The results were described as the percentage of CD54+ lymphocytes and MFI index corresponding density of CD54 molecules on the lymphocyte surface. Statistical analysis was performed using t-Student and U-Mann-Whitney tests. The work was sponsored by KBN 4 P05E 118,15 grant. RESULTS: The percentage of CD54+ lymphocytes in physiological pregnancy compared to nonpregnant women did not differ significantly (56.9 +/- 20.8% vs. 57.2 +/- 14.0%, p = 0.97). The MFI value was increased in pregnant women but in comparison with nonpregnant women did not reach statistical significance (34.7 +/- 35.7 vs. 17.8 +/- 4.3, p = 0.20). The percentage of CD54+ lymphocytes in TH group compared to normal pregnant women did not differ significantly (52.2 +/- 18.6% vs. 56.9 +/- 20.8%, p = 0.58) but MFI value was significantly increased (100.6 +/- 81.5 vs. 34.7 +/- 35.7). In PE group compared to normal pregnant women the percentage of CD54+ lymphocytes as well as MFI value were significantly increased (CD54+: 70.8 +/- 12.9% vs. 56.9 +/- 20.8%, p < 0.05; MFI: 170.8 +/- 91.7 vs. 34.7 +/- 35.7, p < 0.0005). CONCLUSIONS: 1/expression of ICAM-1 molecule on peripheral blood lymphocytes studied "in vitro" during normal pregnancy is not different in comparison to the nonpregnant state, but 2/ in pregnancy complicated with PIH is significantly increased, especially in PE, 3/described changes are a sign of the lymphocyte activation and may be responsible for endothelial destruction observed in PIH.     

Serum concentration of soluble vascular-cellular adhesion molecule-1 (VCAM-1) and expression of its receptor VLA-4 on the surface of peripheral blood and decidual lymphocytes of preeclamptic women

INTRODUCTION: Vascular-cellular adhesion molecule-1 (VCAM-1) overexpression on the cells' surface is stimulated by pro-inflammatory cytokines, bacterial endotoxins, reactive oxygen species and lipid peroxides. In the serum also the soluble form of VCAM-1 (sVCAM-1) is present. The beta 1-integrin family molecule VLA-4 (CD49d) is natural ligand for VCAM-1. Increased concentrations of sVCAM-1 as well as overexpression of VLA-4 were observed during inflammatory reaction. THE AIM: To study sVCAM-1 serum concentrations and CD49d+ subpopulations of peripheral blood and decidual lymphocytes of the 3rd trimester healthy and preeclamptic women. MATERIALS AND METHODS: The study groups: n = 21 healthy pregnant women, n = 33 preeclamptic women (preeclampsia defined as blood pressure > 140/90 mmHg with proteinuria > 0.3 g/24 h). Clinical states of known pathogenesis which could possibly interfere with values of studied parameters were excluded. Exclusion criteria were also uterine contractions and premature rupture of amniotic membranes. Decidua was collected exclusively during elective caesarean sections. The sVCAM-1 concentration (ng/ml) was estimated using ELISA procedure, while percentage (%) of CD49d+ lymphocytes in the whole blood and homogenized decidual tissue, using flow cytometry. The results were presented as median value with 25% and 75% cut off values. Statistical analysis was performed with U-Mann-Whitney test (p < 0.05). RESULTS: Preeclamptic women presented with increased sVCAM-1 serum concentrations (532.5 (400.0/605.0) ng/ml vs. 387.0 (320.0/416.5) ng/ml, p < 0.0005), increased (%) of CD49d+ peripheral blood (92.0 (88.0/96.0)% vs. 52.9 (47.5/55.8)%, p < 0.0000001) and CD49d+ decidual lymphocytes (88.0 (84.0/90.0)% vs. 80.5 (74.0/85.6)%, p < 0.05). CONCLUSION: Described change suggest that immunological mechanisms similar to inflammatory reaction could be involved in pathogenesis of preeclampsia in peripheral blood as well as locally inside maternal-fetal interface.     

Parameters of peripheral whole blood neutrophil activity in women with pregnancy induced hypertension

OBJECTIVES: Pregnancy induced hypertension is believed to be a state of neutrophil overactivity, however all previous studies were done on isolated cells. DESIGN: To study neutrophil activity in whole blood of PIH women. MATERIALS AND METHODS: Neutrophil activity was estimated without isolation, in peripheral whole blood of 23 PIH women and 26 normal pregnant controls. The chemiluminescence test was performed without any stimulation and upon stimulation of neutrophils with fMLP, OZ and PMA, before and after pre-activation with TNF-alpha. The results were corrected according to the haemoglobin concentration and (%) of neutrophils. The percentage of whole blood neutrophils indicating expression of selectins CD18, CD11b, integrin CD62L and mean fluorescence intensity (MFI) of these molecules were studied on flow-cytometry. RESULTS: The study revealed that neutrophil chemiluminescence was not significantly higher in PIH women and after correction coefficient used it was even lower in PIH patients. TNF-alpha preactivation had no influence on chemiluminescence results. Expression of CD11b expressed as MFI value was significantly increased while that of CD62L, expressed as (%) of positive cells and MFI value--decreased in PIH patients. CONCLUSIONS: Changes of neutrophil CD11b and CD62 expression indicate increased activity of these cells in PIH women, however low production of reactive oxygen species estimated by corrected chemiluminescence test especially after TNF-alpha pre-activation, indicates that this form of their reactivity is rather "exhausted" during PIH.     

The role of peripheral blood lymphocyte subpopulations in differentiation between preeclampsia and transient hypertension

OBJECTIVES: Hypertension is the most frequent complication of pregnancy after 24th week of gestation, occurring in 8% of pregnancies and being the main cause of perinatal mortality and morbidity. It is classified as preeclampsia (PE) or transient hypertension (TH). According to some statements PE and TH are distinct syndromes of different pathogenesis. There are even opinions emphasizing that in most cases TH is in fact undiagnosed chronic hypertension. The role of immunological system in pathogenesis of PE is well known but the hypothesis that immunological events are engaged in pathogenesis of chronic hypertension has not been proved so far. Assuming that TH is closer in its pathogenesis to chronic hypertension than to PE it would be possible to differentiate between TH and PE using some immunological tests. If PE and TH are the same, the differences would be insignificant. DESIGN: The aim of this study was to check the hypothesis that peripheral blood lymphocyte subsets analysis is an useful tool in differentiation between PE and TH and confirmation of their distinct origin. MATERIALS AND METHODS: The study groups consisted of 19 pregnant women with PE (mean age 25.5 +/- 2.5 years, mean gestational age 32.5 +/- 2.5 weeks, 84.2% primiparae) and 14 pregnant women with TH (mean age 27.0 +/- 3.0 years, mean gestational age 33.5 +/- 3.0 weeks, 100% primiparae) diagnosed between 30-37 week of gestation. All women were matched according to gestational age and race. They had no renal diseases or chronic hypertension prior to pregnancy neither had any features of them during the study. Exclusion criteria were: uterine contractions, infection and therapy with steroids before blood sampling. PE and TH were defined according to USA National Health Institute criteria. Peripheral blood was obtained by venipuncture. Standard immunofluorescent marking techniques for whole blood with one-step monoclonal antibodies were performed. Lymphocyte subsets (CD19+, CD3+, CD4+, CD8+, CD3-/CD16+/CD56+, CD3+/CD16+/CD56+, CD8+/CD28+, CD4+/CD45RA+, CD4+/CD45RO+, CD3+/CD69+) analysis was done with flow-cytometer FACSCalibur with 488 nm argon laser. The lymphocyte cells region was chosen with LeucoGATE and analysis performed with SimulSET v.3.1 programme. Statistical analysis was based on Student T test. RESULTS: The differences in peripheral blood lymphocyte subsets composition between PE and TH were insignificant. CONCLUSION: Is that on the basis of peripheral blood lymphocyte subsets analysis PE and TH despite different clinical symptoms seem to have common pathogenesis. However there is possibility that changes observed in peripheral blood are not significantly different in PE and TH because of their low importance for immunopathogenesis.     

Changes in serum concentrations of tumor necrosis factor alpha and adhesion molecules in normal pregnant women and those with pregnancy-induced hypertension

AIM: To study whether serum tumor necrosis factor alpha gene (TNFalpha) and adhesion molecule levels are indicators of the onset of pregnancy-induced hypertension (PIH), we compared levels of these molecules between normal pregnant women and PIH patients from the first to the third trimester. METHODS: We serially measured serum concentrations of TNFalpha, soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble P-selectin (sP-selectin) using enzyme immunoassay kits in 10 normal pregnant women and 10 pregnant women who developed PIH late in gestation. RESULTS: Serum TNFalpha, sICAM-1 and sE-selectin levels in PIH affected women were significantly higher from the first trimester compared with those in normal pregnancy. sVCAM-1 and sP-selectin levels were not significantly changed. CONCLUSION: Serum TNFalpha, sE-selectin and sICAM-1 levels might be effective indicators of the onset of PIH.     

Adhesion molecules,activin and inhibin—candidates for the biochemical prediction of hypertensive diseases in pregnancy?

Background The aim of the prospective study was to compare standard parameters as Doppler ultrasound and 24-h blood pressure measurement with possible maternal serological markers regarding their prognostic value in predicting hypertensive diseases in pregnancy.Materials Twenty-four-hour blood pressure measurement was performed before and after 32+0 gestational week in 57 pregnant women with either chronic hypertension (n=13), preeclampsia (n=21), pregnancy-induced hypertension (PIH; n=12) or normotension (n=11). Blood samples were taken and the concentrations of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), activin A and inhibin A were determined as well as serum uric acid, creatinine, total serum protein and serum albumin. Doppler ultrasound of the uterine arteries was examined before 32+0 gestational week in the same patients. For the statistical evaluation Kruskal-Wallis-Test and Mann-Whitney-U-Test were performed. Differences in the predictive value were evaluated by receiver-operating characteristics.Results VCAM-1 was significantly elevated in women developing hypertensive diseases as compared to normotensive women (preeclampsia: p<0.001; PIH: p<0.05; chronic hypertension: p<0.001). In early pregnancy activin A and inhibin A were significantly higher in preeclamptic patients than in the other groups (activin A: normotension: p<0.005; PIH: p<0.001; chronic hypertension: p<0.005) (inhibin A: normotension: p<0.005; PIH: p<0.001; chronic hypertension: p<0.01), thus suggesting them to be specific markers for the development of preeclampsia. Mean arterial pressure was significantly elevated in preeclampsia (p<0.001) and chronic hypertension (p<0.005) as compared to normotensives.Conclusion Twenty-four-hour blood pressure monitoring with determination of mean arterial pressure and measurement of VCAM-1, activin A and inhibin A as serum parameters can be suggested as useful tests in the specific prediction of different types of hypertensive diseases in pregnancy.Abbreviations AUC Area under the curve - ELISA Enzyme-linked immunosorbent assay - ICAM-1 Intercellular adhesion molecule-1 - MAP Mean arterial pressure - PI Pulsatility index - PIH Pregnancy-induced hypertension - ROC Receiver-operating characteristic - s Soluble - SD Standard deviation - VCAM-1 Vascular cell adhesion molecule-1 - g.w. Gestational week     

Evaluation of some neutrophil adhesion molecules in pregnancy complicated by diabetes mellitus type 1

The effective functions of human peripheral blood neutrophil are modulated by regulatory molecules depending on receptor agonists and adhesion molecules. OBJECTIVES: Evaluation of percentage of neutrophil adhesion molecules in pregnancy of diabetic mothers as well as their expression on peripheral blood neutrophils. MATERIAL: A-12 pregnant diabetic women at 7-13 and 34-36 weeks of first gestation, B-11 healthy pregnant women match for gestation, age and parity; C-11 healthy non-diabetic women; D-14 diabetic, non-pregnant women. METHODS: MFI expression and percentage of CD18, CD11b, CD62L and CD54 were evaluated resting and activated by 30 min., fMLP preincubation using monoclonal antibodies anti-CD11b and anti-CD62L, employing Flow Cytometer FACSCalibur with computer program CELLquest. RESULTS: Expression of CD11b and CD18 receptor on leukocyte of A, B, D groups was higher spontaneous and after stimulation by fMLP in I-st trimester compare to group C and then lowered in IIIrd. The significant difference in CD62L percentage was noticed resting and activated neutrophils in group A, which was lower compared to C and expression of CD62L on peripheral blood neutrophils was higher in group B compared to other studied groups in Ist trimester. There was an increase in expression of CD54 on resting neutrophils of group D when compared with C. A significant difference between Ist and IIIrd trimester was noticed in group A in expression of CD62L,CD62L/fMLP,CD54 on peripheral blood neutrophils, which were higher in the third trimester. Expression of CD62L was higher in the group A when compared to B. CONCLUSIONS: Diabetes type 1 and pregnancy changed the percentage and MFI of neutrophil adhesion molecules.     

妊娠高血压综合征免疫学发病机制的研究

目的：研究妊娠高血压综合征（妊高征）的免疫学发病机制。方法：通过检测妊高征患者及正常孕妇蜕膜组织细胞培养上清液中白细胞介素－１（ＩＬ－１）、白细胞介素－２（ＩＬ－２）和肿瘤坏死因子－α（ＴＮＦ－α）的活性，分析蜕膜免疫细胞因子的变化与妊高征之间的关系。结果：与正常孕妇相比，妊高征患者蜕膜组织中ＩＬ－１、ＩＬ－２和ＴＮＦ－α的分泌显著升高。结论：蜕膜组织免疫微环境中细胞因子的改变可能是妊高征发病的机制之一     

The role of cytokines in Th1/Th2 balance in pregnant women with transient hypertension

OBJECTIVES: There is growing evidence that Th1/Th2 imbalance in cytokine network may play role in immunopathology of preeclampsia (PE). Normal pregnancy is "Th2 phenomenon" while PE is believed to be caused by Th1-shift. There is few data concerning Th1/Th2 imbalance in transient hypertension of pregnancy (TH). DESIGN: The aim of this study was to check the hypothesis that changes in IFN-gamma and IL-2 (Th1 cytokines) levels are accompanied with deficit in TGF-beta (anti-Th1 cytokine) production in TH. MATERIALS AND METHODS: The study group consisted of 10 pregnant women with TH diagnosed between 30-37 week of gestation (mean age 27.0 +/- 3.0 years, mean gestational age 33.5 +/- 3.0 weeks) and 10 women with uncomplicated pregnancy (mean age 26.0 +/- 3.5 years, mean gestational age 35.5 +/- 1.5 weeks). All women were primigravidae matched according to gestational age and race. They had no diabetes mellitus and renal diseases prior to pregnancy neither had any features of them during the study. They had no hypertension before pregnancy. Exclusion criteria were: uterine contractions, infection and therapy with steroids before blood sampling. TH was defined according to USA National Health Institute criteria. Peripheral blood lymphocytes (PBL) were cultured for 72 hours in standard 1640 RPMI medium enriched with 20% FCS, L-glutamine, antibiotics (Sigma) and mitogen phytohemaglutynine (PHA) (Sigma). Cytokine levels were estimated in culture supernatants by using standard ELISA kits according to the indications of the producer (R&D). Statistical analysis was performed with Student-T test. RESULTS: In TH group the levels of IL-2 were higher compared with control group but the differences did not reach statistical significance (4.5 vs. 1.56 pg/ml, t = -1.00, p < 0.1). The same referred to IFN-gamma levels (754.0 vs. 771.0 pg/ml, t = -0.04, NS). However, TGF-beta levels were significantly lower in TH group compared with control group (2459.2 vs. 4156.4 pg/ml, t = -1.47, p < 0.05). Conclusion is that there is a significant deficit of TGF-beta production in peripheral blood lymphocytes of women with TH studied "in vitro". This may contribute to Th1-shift seen in TH similarly to PE.     

妊娠高血压综合征患者蜕膜组织中免疫相关细胞变化的研究

目的研究妊高征的免疫学发病机制。方法通过对妊高征患者及正常孕妇胎盘蜕膜组织中免疫相关细胞进行光镜观察,测定淋巴细胞转化率,探讨蜕膜免疫相关细胞的变化与妊高征之间的关系。结果蜕膜中大颗粒淋巴细胞及凋亡细胞显著增多,ＣＤ＋５７细胞数量及ＣＤ＋４与ＣＤ＋８比例上升,淋巴细胞转化率明显升高。结论蜕膜中免疫相关细胞参与了妊高征的免疫学发病机制。     

MTHFR基因多态性与妊高征的遗传易感性研究

目的 :探讨N5,N10 亚甲基四氢叶酸还原酶 (MTHFR)基因多态性与妊高征(PIH)的关系。方法 :运用多聚酶链反应 限制性内切酶片段长度多态性 (PCR RFLP)技术检测 99例PIH及 5 4例对照组的MTHFR基因多态性。结果 :PIH患者的MTHFR基因CC、CT、TT基因型频率分别为 5 3.5 %、31.3%、15 .2 % ,对照组的CC、CT、TT基因型频率分别为 4 6 .3%、4 4.4 %、9.3% ,两组的CT基因型频率差异有显著性 (P <0 .0 5 ) ,CT基因型与重型PIH有关。结论 :MTHFR基因CT基因型可能是PIH的危险因子 ,CT基因型与重型PIH相关     

妊高征患者蜕膜组织中淋巴细胞转化率及细胞因子活性的变化

目的:研究妊娠高血压综合征(简称妊高征)的免疫学发病机制。方法:通过测定妊高征患者及正常孕妇蜕膜组织中淋巴细胞转化率,检测细胞培养液上清中白细胞介素-1(IL-1)、白细胞介素-2(IL-2)及肿瘤坏死因子α的活性,探讨妊高征的免疫学发病机制。结果:实验组淋巴细胞转化率、IL-1、IL-2、TNF-α活性均比对照组高,有显著统计学意义。且IL-2活性升高与淋巴细胞转化率存在明显的直线正相关。结论:蜕膜组织中的细胞因子异常升高及T细胞可能处于高免疫激活状态参与了妊高征的免疫学发病机制。     

Tissue concentrations of endothelial cell adhesion molecules in the lower uterine segment during term parturition

OBJECTIVE: To determine the concentration of endothelial cell adhesion molecules in the lower uterine segment during parturition at term. METHODS: We analyzed protein extracts from the lower uterine segments of 38 women who had nonelective cesareans at term. We measured concentrations of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and platelet endothelial cell adhesion molecule-1 by enzyme-linked immunosorbent assay. Subjects were grouped according to cervical dilatation (less than 2 cm, n = 10; 2 to less than 4 cm, n = 9; 4-6 cm, n = 9; more than 6 cm, n = 10) and duration of labor (up to 6 hours, n = 14; 6-12 hours, n = 10; 12-24 hours, n = 9; longer than 24 hours, n = 5) at the time of cesarean. RESULTS: The median concentration of intercellular adhesion molecule-1 increased significantly with increasing dilatation (from 2.24 ng/mg total protein at less than 2 cm to 6.73 ng/mg at 4-6 cm) and increasing duration of labor (from 2.53 ng/mg up to 6 hours to 5.90 ng/mg at 12-24 hours). However, this study did not have adequate statistical power to identify differences in concentrations of the other endothelial adhesion molecules. CONCLUSION: The results indicate that parturition at term is associated with expression of intercellular adhesion molecule-1.     

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.     

Hemodynamic Profile of Mild Pregnancy Induced Hypertension

An echocardiographic assessment of hemodynamics was performed in normotensive pregnant women, and in two categories of patients with mild pregnancy-induced hypertension (PIH): those with preeclampsia (PE, proteinuria 0.3g/24 hours) (n=23) and those with gestational hypertension (GH, proteinuria < 0.3g/24 hours) (n=22). The purpose of the study was to establish whether the two subsets of patients with PIH differ in respect to hemodynamics. Patients with PE had significantly lower stroke volume index and cardiac index than patients with GH, and normotensive pregnant women. Despite similar values of mean blood pressure, patients with PE had systemic vascular resistances higher than GH patients. In the PE group mean fetal weight was lower and the incidence of small for gestational age infants was higher than in the GH group.

The differences in hemodynamic profile in patients with preeclampsia and in woman with gestational hypertension suggest that they represent two distinct pathophysiologic entities. PIH with proteinuria, despite “mild” elevation of blood pressure is predominantly associated with high systemic vascular resistance, which may explain poorer fetal outcome in this group of patients.     

Specific decidual CD14(+) cells hamper cognate NK cell proliferation and cytolytic mediator expression after mucin 1 treatment in vitro

Mucin 1 (MUC1) forms a glycocalyx on the surface of decidual epithelial cells that needs to be removed for successful embryo attachment. We investigated whether MUC1 affects human early pregnancy decidual CD14(+) cells and their interactions with cognate decidual natural killer (NK) cells. FITC-dextran internalisation, surface and intracellular antigen levels, and proliferation of CD14(+) and/or CD56(+) cells were analysed by flow cytometry. Magnetic separation was used to purify CD56(+) and CD14(+) cells. Uncultured CD14(+) cells expressed a negligible percentage of CD1a and CD83 molecules. They expressed lower levels of CD16, and higher levels of endocytic mannose receptors (MR), dendritic cell-specific intercellular adhesion molecule grabbing non-integrin (DC-SIGN), proinflammatory chemokine CC receptor 5 (CCR5), and CD163 receptor, than their peripheral blood counterparts. Lipopolysaccharide stimulation did not affect FITC-dextran internalisation in CD14(+) cells. MUC1 bound and internalised, in a dose-dependent manner, the carbohydrate recognition domain of MR, increasing the decoy IL-1 receptor type II and decreasing IL-15 expression in CD14(+) cells. In the presence of MUC1-treated macrophages, the expression levels of the proliferation and cytotoxic mediators (perforin, Fas ligand and TNF-related activation-induced ligand or TRAIL) was attenuated, while that of the anti-inflammatory chemokine CCL17 was increased, in NK cells compared with untreated macrophages. In conclusion, MUC1 supports the alternative activation of tissue-specific CD14(+) cells, and may restrict proliferation of NK cells and regulate their content of cytotoxic mediators. Based on the experiments with first-trimester decidual cells in vitro, we conclude that removing MUC1 from decidual tissue might help control trophoblast invasion by NK cells.     

妊娠高血压综合征合并胎儿生长受限胎盘组织血管细胞粘附分子1的表达

目的：探讨血管细胞粘附分子1（vascular cell adhesion molecule-1,VCAM-1)在妊娠高血压综合征（简称妊高征）合并胎儿生长受限（fetal growth restriction,FGR)发病过程中的作用。方法：采用免疫组化法测定30例妊高征合并FGR患者、28例非妊高征合并FGR及30例正常妊娠者胎盘组织中血管内皮及滋养细胞的VCAM－1表达。结果：妊高征合并FGR组胎盘底蜕膜内血管内皮VCAM－1的表达阳性率（80％）及表达强度（＋＋＋）14例，与正常妊娠组25％（＋＋＋）0例及非妊高征合并FGR组155％（＋＋＋）0例相比明显增高（P＜0．005），而前两者间无显著差异，随妊高征病情加重，其表达强度逐渐增强；胎盘绒毛毛细血管VCAM－1阳性表达强度妊高征合并FGR组（73．3％）和非妊高征FGR组（67．8％）明显增强，与正常组（10％）相比差异有显性（P＜0．005）；所有GFR患者胎盘滋养细胞VCAM－1表达强度明显降低（妊高征FGR为0％，非妊高征FGR组3．6％，正常组40％），并且在妊高征组随妊高征病情加重其表达强度急剧减低。结论：胎盘血管内皮及绒毛滋养细胞异常表达的VCAM－1参与了妊高征引起FGR的病理生理过程，可以作为判定妊高征对胎盘损伤程度的一个指标。     

Lymphocyte subset distribution and cytokine secretion in third trimester decidua in normal pregnancy and preeclampsia

BACKGROUND: Excessive Th1 activity in peripheral blood plays a probable role in the pathogenesis of preeclampsia. The aim of the study was to investigate whether disturbed local immune reactions are also present in decidua. METHODS: Flow cytometric analysis of CD3, CD19, CD56/CD16, CD4, CD8, CD4/CD29, CD4/CD45RA, CD4/CD45RO, CD8/CD28, CD3/CD69 lymphocyte subsets isolated from third trimester decidua of pregnants with preeclampsia (n=21) and pregnant controls (n=11) subjected to elective caesarean sections. Spontaneous and phytohemaglutynine stimulated "in vitro" secretion of IL-2, IL-4, IL-6, IL-10, IL-12, IFN-gamma and TGF-beta by decidual lymphocytes was studied by ELISA. For the statistical significance of differences between the groups the U Mann-Whitney test was performed (confidence interval P<0.05). RESULTS: Preeclamptic patients were characterized with an increased percentage of the CD3-/CD56+CD16+, CD8+/CD28+ and decreased percentage of CD3+, CD19+, CD4+/CD45RA+ lymphocytes. The profile of secreted cytokines shifts in favor of Th1 activity (extremely high IFN-gamma and low IL-6 and IL-10 secretion). Decidual IL-12 secretion in preeclamptic patients is decreased compared to controls. CONCLUSION: Changes in NK and T lymphocyte subsets followed with Th1 cytokine IFN-gamma over-activity, could affect local immunoregulatory mechanisms in third trimester decidua of preeclamptic patients.     

Significance of the renin-angiotensin-aldosterone system for pathogenesis and early diagnosis of pregnancy-induced hypertension with special reference to mineralocorticoid receptors

OBJECTIVE: In women with pregnancy-induced hypertension (PIH) the density of mineralocorticoid receptors (MR) in human mononuclear leukocytes (HML) is reduced compared with healthy pregnant women. The same applies to plasma levels of aldosterone and 18-hydroxycorticosterone. In this study, we investigated whether alterations of these parameters preceded the development of clinical symptoms and, therefore, might be potential predictors of PIH involved in the pathogenesis. PATIENTS AND METHODS: In eighty-four women belonging to the risk-group for PIH but not showing any symptoms neither of PIH nor preeclampsia (PE) we characterized prospectively before the onset of disease in the second trimester of pregnancy mineralocorticoid receptor status in HML and steroid plasma levels of aldosterone and its precursors as well as cortisol through radioimmunoassay. RESULTS: 15 women developed PIH, three of which developed PE. Neither in the density of MR nor in the affinity the women that developed PIH showed any difference from healthy women. Steroid plasma levels were identical as well. CONCLUSION: We conclude that a reduction of mineralocorticoid receptors does not precede PIH within the peripheral blood. But still one can assume that the RAAS may be involved in the pathogenesis of PIH, possibly on a local level within the placenta or as a secondary change, initiated by still unknown factors.     

白细胞介素-6及其mRNA与妊高征发病的关系

目的 探讨白细胞介素－６（ＩＬ－６）及其ｍＲＮＡ与妊高征发病的关系。方法 应用逆转洋－聚合酶链反应（ＲＴ－ＰＣＲ）技术,检测５７例妊高征患者（妊高征组）及１５例正常妊娠妇女（正常妊娠组）母血白细胞及胎盘ＩＬ－６ｍＲＮＡ表达,同时采用酶联免疫吸附试验（ＥＬＡＳＡ）法检测母血及羊水中ＩＬ－６含量。结果（１）妊高征组母血ＩＬ－６及其ｍＲＮＡ含量随病中重呈升高趋势,与正常妊娠组比较,差异有极显著性,胎盘Ｉ