Neutrophil Activation Induced by Placental Factors in Normal and Pre-eclamptic Pregnancies In Vitro

Wang, Y.; Gu, Yang; Philibert, Lisa; Lucas, Michael J.

doi:10.1053/plac.2001.0691

Cited by 44 publications

(37 citation statements)

References 21 publications

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“…24 TNF-␣, platelet-activating factor, and syncytiotrophoblast microvesicles are among the factors that may contribute. 7,25,26 However, the results presented do not favor this hypothesis because the increased sensitivity persisted in EBV-immortalized lymphoblasts when the environmental (plasma) factors were removed. This suggests that women with preeclampsia may be genetically predisposed to have an NADPH oxidase that is more sensitive to agonist stimulation, similar to that of a "primed" cell.…”

Section: Discussionmentioning

confidence: 66%

NADPH Oxidase Activity in Preeclampsia With Immortalized Lymphoblasts Used as Models

et al. 2003

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Abstract-Upon activation, neutrophils release reactive oxygen species that are believed to contribute to the widespread manifestation of preeclampsia. Neutrophils have an NADPH oxidase enzyme that catalyzes the production of reactive oxygen species. Little is known about the manifestations of the activated response and the upstream signaling pathways that regulate this process in preeclampsia. It is hypothesized that genetic factors may contribute to the release of reactive oxygen species and consequently the pathophysiology of the disease. We used Epstein-Barr virus-immortalized lymphoblasts from third-trimester, preeclamptic, postpartum preeclamptic women and their respective control subjects to assess NADPH oxidase-mediated reactive oxygen species production by using luminol-derived chemiluminescence and dihydrorhodamine-123 fluorescence. There was no effect of pregnancy status on the lymphoblast phorbol ester-stimulated luminol chemiluminescence area under the curve. However, lymphoblasts from preeclamptic patients had significant elevation of the lymphoblast phorbol ester-stimulated luminol area under the curve (F statistic 10.922, PϽ0.002). Similar findings were evident with dihydrorhodamine-123. No differences were revealed between preeclamptic and control cells when measuring the abundance of the phox proteins using Western blotting. Studies with genistein and tyrphostin implicated tyrosine kinase-dependent mechanisms in the control of NADPH oxidaseassociated increased reactive oxygen species production in preeclampsia. These data show that preeclampsia is associated with a predisposition to increased agonist-stimulated NADPH oxidase-mediated reactive oxygen species production. The enhancement of reactive oxygen species generation may be important in mediating the endothelial dysfunction seen in preeclampsia.

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Section: Discussionmentioning

confidence: 66%

NADPH Oxidase Activity in Preeclampsia With Immortalized Lymphoblasts Used as Models

et al. 2003

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“…Preeclampsia is defined severe if one or more of the following criteria is present: maternal blood pressure ≥160/110 mmHg; proteinuria >3+ or >5 g/24 h; oliguria of less than 500 ml in 24 h; intrauterine growth restriction, and presence of persistent headache or visual disturbances. Preeclamptic placental conditioned medium was prepared as previously described [9,15,16]. Briefly, villous tissue, excluding basal plates and fetal membranes, was incubated with serum free Dulbecco's Modified Eagles Medium (DMEM, Sigma Chemical Inc., St Louis, MO) for 48 h. At the end of incubation, the culture medium was collected and stored at -70 °C until use.…”

Section: Preparation Of Placental Conditioned Mediummentioning

confidence: 99%

Contractility of Placental Vascular Smooth Muscle Cells in Response to Stimuli Produced by the Placenta: Roles of ACE vs. Non-ACE and AT1 vs. AT2 in Placental Vessel Cells

Benoit

Zhang

et al. 2008

Placenta

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Our previously published work has shown that non-ACE angiotensin II (Ang II) generating system is dominate in the placenta and may play a critical role in regulation of placental vascular contractile function. In the present study, using a collagen gel contraction assay we further studied contractility of placental vascular smooth muscle cells (VSMCs) in response to factors produced by preeclamptic (PE) placentas. Placental VSMCs/type-1 collagen gels were incubated with PE placental conditioned medium in the presence or absence of inhibitors or receptor blockers. Captopril (an ACE inhibitor), chymostatin (a non-ACE chymase inhibitor), losartan (an AT1 receptor blocker) and PD123,319 (an AT2 receptor blocker) were used to study the specific ACE vs. non-ACE and AT1 vs. AT2 effects on placental VSMC contractility, respectively. Our results showed that chymostatin, but not captopril, and PD123,319, but not losartan, significantly attenuated placental VSMC/collagen gel contraction, p < 0.01, respectively. The inhibitory effects of chymostatin and PD123,319 were dosedependent. Our results suggest that chymase, a non-ACE Ang II generating enzyme, may contribute significantly to Ang II generated in the placenta vascular tissue and that the AT2 receptor may play an important role in the regulation of Ang II induced contractility of placental VSMCs. These results provide new insights into Ang II generation and Ang II receptor regulation of vessel contractile function in the placental vasculature. These results also suggest the potential role of increased chymase activity and altered AT2 receptor function in placental related pregnancy disorders such as preeclampsia and IUGR.

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“…Placental conditioned media (CM) were prepared from villous tissue explant culture from the placentas of preeclamptic patients as previously described [29,30]. Briefly, placentas were obtained immediately after delivery from preeclamptic pregnancies.…”

Section: Conditioned Medium Preparationmentioning

confidence: 99%

Vasoreactivity of Chorionic Plate Arteries in Response to Vasoconstrictors Produced by Preeclamptic Placentas

2007

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Inadequate blood flow and increased vasoconstriction of the placenta contribute to pregnancy associated disorders such as preeclampsia (PE). Because placental vessels lack autonomic innervation, humoral effects of the placenta must play critical roles in regulation of fetal-placental vascular contractility. In this study, we examined the nature of humoral factors produced by PE trophoblasts on placental vessel contractility using an organ bath perfusion model. Vasomotor responses were studied in vitro using placental chorionic plate arteries. Vessel rings from third branch chorionic plate arteries were dissected from human placentas following normal or PE delivery. The arterial rings were equilibrated in Krebs Henseleit buffer and exposed to placental conditioned medium, which was prepared by culture of villous tissue from PE placentas. Receptor antagonists for angiotensin II (ANG II), thromboxane (TX), and endothelin (ET) were used to determine which humoral factor produced by placental tissue (trophoblasts) was more effective in promoting vasoconstriction. The role of angiotensin converting enzyme (ACE) and non-ACE ANG II generating enzymes in regulation of placental vasomotor tone were also investigated. A total of 80 arterial rings from 48 placentas were studied. Our results showed: 1) enhanced vasomotor tone in arteries from PE placentas compared to those from normal placentas; 2) PE-CM induced vaso-constrictive activity could be partially attenuated by receptor antagonists for TX, ANG II and ET, respectively; and 3) chymostatin (a chymase inhibitor) produced a stronger inhibitory effect than captopril (ACE inhibitor) on PE conditioned medium induced vasoconstriction. Our data demonstrate increased vasocontractility in PE placentas and suggest that the non-ACE pathway is probably a major source of ANG II produced in the human placenta.

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Neutrophil Activation Induced by Placental Factors in Normal and Pre-eclamptic Pregnancies In Vitro

Cited by 44 publications

References 21 publications

NADPH Oxidase Activity in Preeclampsia With Immortalized Lymphoblasts Used as Models

NADPH Oxidase Activity in Preeclampsia With Immortalized Lymphoblasts Used as Models

Contractility of Placental Vascular Smooth Muscle Cells in Response to Stimuli Produced by the Placenta: Roles of ACE vs. Non-ACE and AT1 vs. AT2 in Placental Vessel Cells

Vasoreactivity of Chorionic Plate Arteries in Response to Vasoconstrictors Produced by Preeclamptic Placentas

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