A selective increase in plasma soluble vascular cell adhesion molecule-1 levels in preeclampsia.

PROBLEM: The study was conducted to determine whether altered plasma levels of soluble intercellular adhesion molecule (ICAM)-1 and soluble vascular cell adhesion molecule (VCAM)-1 are involved in the pathogenesis of preeclampsia. METHOD OF STUDY: Maternal plasma samples were collected from 20 patients with preeclampsia, 20 matched normotensive patients with uncomplicated pregnancies. and ten healthy nonpregnant women. Samples were assayed for soluble VCAM-1 and soluble ICAM-1 by specific enzyme-linked immunosorbent assay. RESULTS: Both soluble VCAM-1 and soluble ICAM-1 were detectable in the plasma of all preeclamptic, normotensive pregnant, and nonpregnant women. The mean plasma level of soluble VCAM-1 was significantly higher in preeclamptic women compared to normotensive pregnant women (1831 ng/mL +/- 534 ng/mL vs. 1254 ng/mL +/- 386 ng/mL, respectively; P < 0.05). However, the plasma level of soluble VCAM-1 was unchanged during the third-trimester of normal pregnancy compared to nonpregnant women. The mean plasma level of soluble ICAM-1 in preeclamptic and normotensive pregnant women were increased when compared to nonpregnant women. However, the mean plasma level of soluble ICAM-1 was comparable in women with preeclampsia and normotensive pregnancy. CONCLUSIONS: The selective increased plasma levels of soluble VCAM-1 in patients with preeclampsia provide evidence for endothelial activation and suggest distinct pathways for neutrophil and endothelial activation in preeclampsia.     

Maternal Levels of Prostacyclin,Thromboxane, ICAM,and VCAM in Normal and Preeclamptic Pregnancies

Citation Lewis DF., Canzoneri BJ., Gu Y, Zhao S, Wang Y. Maternal Levels of Prostacyclin, Thromboxane, ICAM, and VCAM in normal and preeclamptic pregnancies. Am J Reprod Immunol 2010; 64: 376–383 Problem To evaluate whether impaired endothelial function and endothelial inflammatory response occur in parallel in the women with preeclampsia. Method of Study Venous blood was drawn from normal (n = 40) and severe preeclamptic (sPE) (n = 40) pregnant women when they were admitted to the L&D Unit and 24 hrs after delivery. Plasma and serum samples were extracted and measured for 6‐keto PGF1α and TXB₂ (stable metabolites of PGI2 and TXA2), and intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) by ELISA. Data are analyzed by Mann–Whitney test and paired t‐test. The statistical significance is set as P < 0.05. Results Plasma 6‐keto PGF1α levels were significantly reduced at admission and 24 hr after delivery in sPE compared to normal pregnant controls, P < 0.01. The ratio of 6‐keto PGF1α and TXB₂ was significant less in sPE than that in normal pregnant controls before delivery. There was no significant difference for ICAM and VCAM levels between normal and patients with sPE before and after delivery. Conclusion Maternal 6‐keto PGF1α levels and the ratio of 6‐keto PGF1α and TXB₂ were decreased in patients with sPE compared to normal pregnant controls. In contrast, maternal ICAM and VCAM levels were not different between the two groups. These data suggest that serum ICAM and VCAM levels may not be sensitive inflammatory biomarkers for preeclampsia.     

Leukocyte Activation and Circulating Leukocyte-Derived Microparticles in Preeclampsia

Problem  Preeclampsia shows characteristics of an inflammatory disease including leukocyte activation. Analyses of leukocyte-derived microparticles (MP) and mRNA expression of inflammation-related genes in leukocytes may establish which subgroups of leukocytes contribute to the development of preeclampsia.
Method of Study  Blood samples were obtained from preeclamptic patients, normotensive pregnant and non-pregnant controls. sL-selectin and elastase were measured by ELISA. mRNA was isolated from leukocytes and gene expression was determined by multiplex ligation-dependent probe amplification (MLPA). MP were characterized by flow cytometry.
Results  Altered concentrations of sL-selectin and elastase confirmed leukocyte activation in preeclampsia. These leukocytes showed up-regulation of Nuclear Factor of Kappa light chain gene enhancer in B Cells inhibitor (NFκB-1A) and cyclin-dependent kinase inhibitor (CDKN)-1A compared with normotensive pregnant women. interleukin-1 Receptor Antagonist (IL-1RA) and tumor necrosis factor (TNF)-R1 were increased compared with those in non-pregnant controls. Monocyte-derived MP were elevated in preeclamptic patients compared with pregnant women. The numbers of cytotoxic T-cell-derived and granulocyte-derived MP were elevated compared with those of non-pregnant women.
Conclusion  Leukocytes are activated in preeclampsia. A pro-inflammatory gene expression profile is not prominent, although differences in mRNA expression can be detected. Increased levels of particular subsets of leukocyte-derived MP reflect activation of their parental cells in preeclampsia.     

HMGB1+ microparticles present in urine are hallmarks of nephritis in patients with systemic lupus erythematosus

Non‐classical monocytes infiltrate the kidney parenchyma and participate in tissue damage in patients with lupus nephritis (LN). Circulating microparticles (MPs) seem to play critical roles in the activation of monocytes in systemic lupus erythematosus (SLE) patients. This study aims to characterize the phenotypes of MPs and monocyte subsets in LN patients and to determine their potential to discriminate between SLE patients with and without LN. Blood and urine samples from SLE patients were collected. In monocyte subsets from whole blood samples several phenotypic markers were evaluated. MPs were isolated from platelet‐poor plasma and urine by centrifugation. This phenotypic marker characterization was performed using multiparametric flow cytometry. We observed that patients with active LN have lower counts of non‐classical monocytes than do those without renal involvement. All monocyte subsets exhibited lower expression of CX3CR1 and ICAM‐1 in LN than in patients without LN. High frequencies of MP‐HMGB1⁺ and MP‐HLA‐DR⁺ were detected in circulation and urine of LN patients. Although MP‐HMGB1⁺, MP‐HLA‐DR⁺, and MP‐CX3CR1⁺ from urine were able to discriminate between patients with and without LN, only urinary MP‐HMGB1⁺ were different between patients with active and inactive LN. Therefore, these vesicles may be useful as biomarkers of LN.     

Cytotoxic effects of soluble factor in preeclamptic sera on human trophoblasts

Evidence indicating abnormal biological behavior of trophoblasts has been seen in preeclamptic patients, but the mechanism is still unknown. We have previously shown that endothelial injury and neutrophil activation are induced by certain factors in preeclamptic sera. We investigated the effect of sera from eight preeclamptic and 11 normal pregnant women on cellular proliferation and viability of trophoblasts using 3H-thymidine incorporation and the trypan-blue dye exclusion test, respectively. Five of eight preeclamptic sera, but none of the normal pregnant sera, inhibited 3H-thymidine incorporation. The trypan-blue test revealed the sera reduced cellular viability. Gel permeation showed that the greatest growth-inhibitory activity corresponded to a molecular weight of 50 kDa. The serum-mixing test revealed this permeation and inhibitory preeclamptic sera suppressed the growth-promoting activity of normal pregnant sera in a dose-dependent manner. These results suggested the presence of certain factors in some preeclamptic sera that can affect cellular behavior of human trophoblasts.     

Corticosterone treatment of pregnant low dose endotoxin-treated rats: inhibition of the inflammatory response

PROBLEM: Can the endotoxin‐induced inflammatory response, underlying experimental pre‐eclampsia, in pregnant rats be inhibited by corticosterone?
METHOD OF STUDY: On day 10 of pregnancy, rats were implanted with pellets containing 25% corticosterone and 75% cholesterol (n=10) or with 100% cholesterol‐pellets (n=10). On day 14 of pregnancy, rats were infused with either endotoxin (1.0 μg/kg bw) or saline. Three days later, they were sacrificed. Cryostat kidney sections were immunohistologically stained for the presence of neutrophils (PMN) and monocytes (M?) and the expression of inflammation‐associated adhesion molecules.
RESULTS: In cholesterol‐treated rats, endotoxin significantly increased glomerular numbers of PMN and M?, glomerular expression of ICAM‐1 and VCAM‐1 and glomerular numbers of LFA‐1 and VLA‐4‐positive cells as compared with saline. Corticosterone treatment significantly inhibited glomerular infiltration of PMN, M? and LFA‐1 positive cells after endotoxin infusion. It did not affect glomerular ICAM‐1 or VCAM‐1 expression or numbers of VLA‐4 positive cells.
CONCLUSIONS: It is concluded that pre‐treatment with corticosterone inhibits the low dose endotoxin‐induced glomerular inflammatory reaction in pregnant rats, most likely by inhibiting LFA‐1 expression, thereby decreasing the adhesiveness of inflammatory cells for activated endothelial cells.     

Shed membrane particles from preeclamptic women generate vascular wall inflammation and blunt vascular contractility

We investigated the role of microparticles in vascular dysfunction of the multisystemic disorder of preeclampsia in women's omental arteries or mouse arteries. Preeclamptic women displayed increased circulating levels of leukocyte- and platelet-derived microparticles compared with healthy pregnant individuals. Microparticles from preeclamptic, but not healthy, pregnant women induced ex vivo vascular hyporeactivity to serotonin in human omental arteries and mouse aortas. Hyporeactivity was reversed by a nitric-oxide (NO) synthase inhibitor and associated with increased NO production. In the presence of a cyclooxygenase (COX)-2 inhibitor, serotonin-mediated contraction was partially reduced in arteries treated with healthy microparticles but was abolished after treatment with preeclamptic microparticles. This was associated with increased 8-isoprostane production. Preeclamptic microparticles induced up-regulation of inducible nitric-oxide synthase and COX-2 expression, evoked nuclear factor-kappaB activation, and enhanced oxidative and nitrosative stress. Interestingly, the microparticles originating most probably from leukocytes were responsible for the COX-2 vasoconstrictor component of preeclamptic microparticles, whereas those of platelet origin were mainly involved in NO release. Moreover, vascular hyporeactivity was observed in arteries taken from mice treated in vivo with preeclamptic microparticles. This study demonstrates pathophysiological relevance and provides a paradoxical effect of preeclamptic microparticles associated with proinflammatory properties on vessels, leading to enhanced NO and superoxide anion levels and counteraction of increased COX-2 metabolites.     

Interleukin-12 secretion by peripheral blood mononuclear cells is decreased in normal pregnant subjects and increased in preeclamptic patients

PROBLEM: It has been reported that T-helper (Th) 2 dominance in normal pregnancy shifts to Th1 dominance in preeclampsia. Peripheral blood mononuclear cell (PBMC) production of interleukin (IL)-12, which induce Th1 responses, has not been compared between these clinical states. METHOD OF STUDY: Peripheral blood mononuclear cell from 35 non-pregnant women, 35 healthy pregnant women, 12 mildly preeclamptic patients, and 15 severely preeclamptic patients were cultured for 24 hr. IL-12 secretion was determined by enzyme-linked immunosorbent assay (ELISA). Th1/Th2 ratios in PBMC were determined flow-cytometrically, and the amounts of HLA-DR and CD14 expression on the monocytes were obtained by flow cytometry. RESULTS: Peripheral blood mononuclear cell from healthy pregnant subjects secreted less IL-12 than non-pregnant women. PBMC from severely preeclamptic patients secreted more IL-12 than those from healthy pregnant subjects, while IL-12 secretion in mild preeclampsia resembled secretion in normal pregnancy. Th1/Th2 ratios correlated were positively with IL-12. Increased HLA-DR antigens and reduced CD14 expression, suggesting monocyte activation, were observed in preeclamptic patients, although monocyte counts were unchanged. CONCLUSION: Decreased IL-12 secretion by PBMC may cause Th2 dominance in normal pregnancy, while increased IL-12 secretion by activated monocytes may cause Th1 dominance in preeclampsia.     

Monocytes of preeclamptic women spontaneously synthesize pro-inflammatory cytokines

The maternal syndrome preeclampsia is characterized by a generalized inflammatory response with activation of circulating leukocytes and altered levels of inflammatory cytokines. We hypothesized that one potential source of inflammatory cytokines during preeclampsia is the circulating maternal monocytes. By using flow cytometry, we found that the spontaneous intracellular synthesis of IL-1beta, IL-6, and IL-8 in monocytes of preeclamptic women was higher than in normal pregnant and non-pregnant women. The highest levels of cytokines were detected in women with the most abnormal laboratory values. When stimulated with lipopolysaccharide (LPS), the percentage of IL-1beta+ monocytes was lower in preeclampsia (72.6% +/- 8.2 SEM) than in normal pregnancy (90.7% +/- 2 SEM) (P = 0.03) and non-pregnant women (92.5% +/- 1.4 SEM) (P = 0.04) suggesting that monocytes from preeclamptic patients cannot be further stimulated. These results indicate that maternal circulating monocytes represent a source of inflammatory cytokines during preeclampsia.     

Glatiramer acetate attenuates the pro‐migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis

An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell‐bound and soluble AM in the peripheral blood of patients with relapsing–remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)‐1, ICAM‐3, lymphocyte function‐associated antigen (LFA)‐1 and very late activation antigen (VLA)‐4 were assessed in T cells (CD3⁺CD8⁺, CD3⁺CD4⁺), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five‐colour flow cytometry. Soluble E‐selectin, ICAM‐1, ICAM‐3, platelet endothelial cell adhesion molecule (PECAM)‐1, P‐selectin and vascular cell adhesion molecule (VCAM)‐1 were determined with a fluorescent bead‐based immunoassay. The pro‐migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up‐regulation of LFA‐1 (CD3⁺CD4⁺ T cells, B cells), VLA‐4 (CD3⁺CD8⁺ T cells, NK cells), ICAM‐1 (B cells) and ICAM‐3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA‐1 (CD3⁺CD4⁺) and VLA‐4 (CD3⁺CD4⁺, CD3⁺CD8⁺, NK, NK T, monocytes). Further effects included lowering of ICAM‐1 and ICAM‐3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro‐migratory expression profile of cell‐bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects.     

Release of VCAM-1 associated endothelial microparticles following simulated SCUBA dives

Microparticles (MP) are shed into the circulation from endothelium following activation or apoptosis. Vascular cell adhesion molecule-1 (VCAM-1) is expressed on endothelial cells following activation and here we report quantification of VCAM-1 positive microparticles (VCAM + MP) following simulated SCUBA dives, breathing either air or oxygen. VCAM + MP were quantified pre-dive (09:00 and 13:00) and post-dive (+1, +3 and +15 h) on both air and oxygen dives and compared with control samples taken from the same subjects. VCAM + MP followed a similar trend in all experiments, however both dives caused a change in endothelial state, as measured by VCAM + MP. A significant increase in VCAM + MP was observed 1 h post-air dive relative to the control (p = 0.013), which was not observed after the oxygen dive (p = 0.095). Oxidative stress (TBARS) was correlated with VCAM + MP. Data presented highlights the potential of MP as a biological marker of both endothelial state and decompression illness.     

The non-proteolytic house dust mite allergen Der p 2 induce NF-κB and MAPK dependent activation of bronchial epithelial cells

Background House dust mites (HDM) are well‐known as a source of indoor aeroallergens and for causing allergic airway diseases. Some proteolytic HDM allergens are known to activate respiratory epithelial cells to produce pro‐inflammatory mediators, while there is limited knowledge regarding such activity among non‐proteolytic HDM allergens. Objective To investigate whether Der p 2, a major non‐proteolytic allergen of Dermatophagoides pteronyssinus, activates respiratory epithelial cells to produce mediators involved in asthma pathogenesis and to elucidate the mechanism of such activation. Methods The human bronchial epithelial cell line BEAS‐2B, normal human bronchial epithelial (NHBE) cells and the alveolar epithelial cell line A549 were exposed to recombinant Der p 2. Following exposure, we analysed a panel of soluble mediators and cell adhesion receptors involved in asthma pathogenesis by promoting recruitment, survival and binding of inflammatory cells. The involvement of nuclear factor (NF)‐κB and mitogen‐activated protein kinases (MAPKs) was studied using specific inhibitors. Results Der p 2 activated bronchial BEAS‐2B and NHBE cells, but not alveolar A549 cells. In BEAS‐2B cells Der p 2 induced dose‐dependent up‐regulation in both mRNA level and protein secretion of granulocyte‐macrophage colony‐stimulating factor, IL‐6, IL‐8, monocyte‐chemotactic protein‐1 and macrophage inflammatory protein‐3α. Secretion as well as surface expression of intercellular adhesion molecule (ICAM)‐1 was also up‐regulated, which was associated with increased adhesion of monocytes to the epithelial cells. The release of cytokines and chemokines was regulated by NF‐κB and MAPK activation in different ways, while expression of ICAM‐1 was solely dependent on NF‐κB activation. Conclusion These results show that Der p 2 activates respiratory epithelial cells, indicating that this non‐proteolytic allergen, in addition to its immunogenic properties, can aggravate respiratory airway disease by adjuvant‐like activation of the lung epithelium.     

Suppressive Effect of Iron on Concanavalin A‐Induced Multinucleated Giant Cell Formation by Human Monocytes

Immune dysfunction in patients with iron overload has been reported. Iron disturbed CD2 expression on T‐cells, cell‐mediated immunity by Th1 cells and monocyte functions including phagocytosis and natural killer activity. In the present study, we examined the effects of iron and desferrioxamine (DFX, an iron chelator) on generation of multinucleated giant cells (MGC) by human monocytes in vitro. Human monocytes were isolated from venous blood and cultured with concanavalin A (Con A) stimulation with additives, ferric citrate (Fe‐citrate) or sodium citrate (Na‐citrate) or DFX for 4 days. The cells were fixed and subjected to Wright staining. MGC formation was observed under light microscopy. Con A induced MGC formation in a dose‐dependent manner, and reached a plateau after 3 days of incubation. MGC formation was suppressed when Con A‐stimulated monocytes were cultured with the co‐addition of Fe‐citrate but not Na‐citrate only in the early phase of culture (less than 24 hours). DFX also suppressed MGC formation in a dose‐dependent manner. Using flow cytometry analysis, the co‐addition of Fe‐citrate significantly suppressed CD18 (ß2 integrin) and CD54 (ICAM‐1) but not CD11a (α integrin) expression on Con A‐stimulated monocytes. Iron supressed the generation of MGC by human monocytes in vitro. These observations suggested that iron might affect MGC generation by down‐regulation of adhesion molecule expression on monocytes.     

Histochemical Demonstration of Interleukin-2 in Decidua Cells of Patients With Preeclampsia

PROBLEM : The objective of this study was to gain insight into the immunological aspects of preeclampsia. METHOD : The presence of interleukin-2 (IL-2) protein in the decidua was examined in five preeclamptic patients and seven normal pregnant women employing the immunohistochemistry. RESULTS : The decidua cells were strongly stained for IL-2 in four out of five preeclamptic patients, while only very weak, if any, staining was observed in all the uncomplicated pregnant women. CONCLUSIONS : IL-2 was clearly present in decidua cells in the preeclamptic setting, suggesting the possible involvement of immune-activation in the phathophysiology of preeclampsia.     

Circulating cell-derived microparticles in women with pregnancy loss

Citation
Alijotas‐Reig J, Palacio‐Garcia C, Farran‐Codina I, Zarzoso C, Cabero‐Roura L, Vilardell‐Tarres M. Circulating cell‐derived microparticles in women with pregnancy loss. Am J Reprod Immunol 2011; 66: 199–208 Problem To analyze cell‐derived microparticles (cMP) in pregnancy loss (PL), both recurrent miscarriages (RM) and unexplained fetal loss (UFL). Method of study Non‐matched case–control study was performed at Vall d’Hebron Hospital. Cell‐derived microparticles of 53 PL cases, 30 with RM, 16 with UFL, and 7 (RM + UFL), were compared to 38 healthy pregnant women. Twenty healthy non‐pregnant women act as controls. Cell‐derived microparticles were analyzed through flow cytometry. Results are given as total annexin (A5+), endothelial‐(CD144+/CD31+ CD41?), platelet‐(CD41+), leukocyte‐(CD45+) and CD41? c‐MP/μL of plasma. Antiphospholipid antibodies (aPLA) were analyzed according to established methods. Results Comparing PL versus healthy pregnant, we observed a significant endothelial cMP decrease in PL. When comparing RM subgroup with controls, we observed significant decreases in endothelial cMP. When comparing the PL positive for aPLA versus PL‐aPLA‐negative, no cMP numbering differences were seen. Conclusion Pregnancy loss seems to be related to endothelial cell activation and/or consumption. A relationship between aPLA and cMP could not be demonstrated.     

Peripheral Monocyte Expression of the Chemokine Receptors CCR2, CCR5 and CXCR3 is Altered at Parturition in Healthy Women and in Women with Systemic Lupus Erythematosus

Monocytes are precursors of macrophages and recruited to the uterus throughout pregnancy to perform important immunological functions. In this study, we hypothesized that pregnant women have reduced peripheral monocyte expression of chemokine receptors and alterations in PBMC responses to microbial stimuli as an adaption to pregnancy and that these changes are less pronounced in women with autoimmunity. We therefore investigated the chemokine receptor expression, migratory behaviour and responses to microbial stimulation of peripheral monocytes from pregnant women at parturition (n = 13) and from non‐pregnant women (n = 9). In addition, we compared healthy pregnant women with women suffering from SLE (n = 5), a condition with pronounced systemic inflammation increasing the risk for pregnancy complications. We demonstrate that peripheral monocytes are affected by pregnancy with reduced percentages of CCR2+, CCR5+ and CXCR3+ monocytes of both classical (CD16?) and inflammatory (CD16+) subsets and that the trophoblast‐secreted chemokine CCL2/MCP‐1 recruited monocytes of both subsets in vitro. Further, PBMCs from pregnant women had a divergent response to microbial stimulation with lower CCL5/RANTES and higher CCL2/MCP‐1 secretion compared with non‐pregnant women. In addition, pregnant women had lower basal PBMC‐secretion of CCL5/RANTES and higher basal secretion of IL‐10 and CCL2/MCP‐1. Interestingly, the women with SLE responded similar to pregnancy as did healthy women with lower percentages of CCR2+, CCR5+ and CXCR3+ monocytes. However, they had increased expression of CCR5 on CD16+ monocytes and heightened PBMC‐secretion of CCL5/RANTES. In conclusion, our data indicate that monocyte chemokine receptor expression and the chemokine milieu during pregnancy are tightly regulated to support pregnancy.     

Endothelial cells promote stem‐like phenotype of glioma cells through activating the Hedgehog pathway

Microenvironmental regulation of cancer stem cells (CSCs) strongly influences the onset and spread of cancer. The way in which glioma cells interact with their microenvironment and acquire the phenotypes of CSCs remains elusive. We investigated how communication between vascular endothelial cells and glioma cells promoted the properties of glioma stem cells (GSCs). We observed that CD133⁺ GSCs were located closely to Shh⁺ endothelial cells in specimens of human glioblastoma multiforme (GBM). In both in vitro and in vivo studies, we found that endothelial cells promoted the appearance of CSC‐like glioma cells, as demonstrated by increases in tumourigenicity and expression of stemness genes such as Sox2, Olig2, Bmi1 and CD133 in glioma cells that were co‐cultured with endothelial cells. Knockdown of Smo in glioma cells led to a significant reduction of their CSC‐like phenotype formation in vitro and in vivo. Endothelial cells with Shh knockdown failed to promote Hedgehog (HH) pathway activation and CSC‐like phenotype formation in co‐cultured glioma cells. By examination of glioma tissue specimens from 65 patients, we found that the survival of glioma patients was closely correlated with the expression of both Shh by endothelial cells and Gli1 by perivascular glioma cells. Taken together, our study demonstrates that endothelial cells in the tumour microenvironment provide Shh to activate the HH signalling pathway in glioma cells, thereby promoting GSC properties and glioma propagation. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Preeclamptic sera stimulate increased platelet-derived growth factor mRNA and protein expression by cultured human endothelial cells.

Monolayer cultures of human endothelial cells were incubated with pre- and postdelivery sera from five women with preeclampsia and four matched, normal pregnancies. Conditioned media collected from endothelial cells pretreated in vitro with prepartum sera from preeclamptic women contained greater mitogenic activity and elevated levels of platelet-derived growth factor (PDGF)-like peptides than cells exposed to normal pregnancy sera or postpartum preeclamptic sera. Under the same experimental conditions, predelivery preeclamptic sera stimulated greater expression of endothelial cell PDGF-B-chain mRNA than that accumulated in the presence of matched postdelivery sera. By contrast, no differences in endothelial cell PDGF-B mRNA levels were noted when pre- and postdelivery sera from normal parturients were tested. The results suggest that a factor(s) in the blood of preeclamptic women can stimulate the synthesis and release of a potent growth factor and vasoconstrictor from human endothelial cells.