Synthesis of complement proteins in the human chorion is differentially regulated by cytokines

Goldberg, Michael; Luknar-Gabor, N.; Keidar, Ran; Katz, Yitzhak

doi:10.1016/j.molimm.2006.07.298

Cited by 20 publications

(14 citation statements)

References 20 publications

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“…15 FH is also probably synthesized and secreted by trophoblasts. 16 DAF, MCP, and FH downregulate the alternative C3 convertase through binding to C3b, cofactor activity to FI, and/or C3 convertase dissociation. Such control is crucial for the development of the fetus, as outlined by several animal models.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations

Fakhouri¹,

Roumenina²,

François³

et al. 2010

Journal of the American Society of Nephrology

401

395

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In contrast to pregnancy-associated thrombotic thrombocytopenic purpura, the pathogenesis and presentation of pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) remain ill-defined. We conducted a retrospective study to assess the presentation and outcomes of patients presenting with P-aHUS and the prevalence of alternative C3 convertase dysregulation. P-aHUS occurred in 21 of the 100 adult female patients with atypical HUS, with 79% presenting postpartum. We detected complement abnormalities in 18 of the 21 patients. The outcomes were poor: 62% reached ESRD by 1 month and 76% by last follow-up. The risk for P-aHUS was highest during a second pregnancy. Thirty-five women, 26 (74%) of whom had complement abnormalities, had at least one pregnancy before the onset of a non-pregnancy-related aHUS. Outcomes did not differ between patients with pregnancy-related and non-pregnancy-related aHUS. Mutations in the SCR19-20 domains of factor H were less frequent in P-aHUS patients compared with non-pregnancy-related aHUS. Pregnancies in female patients with complement abnormalities (n ϭ 44) were complicated by fetal loss and preeclampsia in 4.8% and 7.7%, respectively. Better understanding of complement dysregulation in pregnancy complications is essential, especially to guide development of pharmacologic agents to modulate this system.

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Section: Discussionmentioning

confidence: 99%

Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations

Fakhouri¹,

Roumenina²,

François³

et al. 2010

Journal of the American Society of Nephrology

401

395

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“…Several C components of both classical and alternative pathways and C regulators are secreted by chorionic tissue and chorion-derived cells and their synthesis is differently regulated by various cytokines (Goldberg et al, 2007). The ability of some of these cytokines to up-regulate local production of C components and regulators in normal pregnancy is critical to neutralize invading pathogens and also to protect the fetus from attack by the maternal immune system.…”

Section: Production Of C Components and Regulators At The Feto-maternmentioning

confidence: 99%

The Complement System at the Embryo Implantation Site: Friend or Foe?

2012

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An inflammatory-like process and vascular remodeling represent the main changes that occur in decidua in the early phase of pregnancy. These changes are partly induced by trophoblast cells that colonize the decidua and are also contributed by the complement system, which can easily be activated as a result of tissue remodeling. Local control by several complement regulators including surface-bound and soluble molecules is critical to prevent complement-mediated tissue damage in normal pregnancy. C7 expressed on the endothelial cells (ECs) surface has been recognized as a novel complement regulator involved in the control of the proinflammatory effect of the terminal complement complex. The protective role of placental complement regulators in pregnancy is underscored by the recent finding of an association of preeclampsia with mutations in the genes encoding for some of these proteins. Complement components produced at feto-maternal interface serve an important function in placental development. C1q synthesized by decidual ECs and expressed on the cell surface is particularly important in this regard because it acts as a molecular bridge between endovascular trophoblast and ECs. C1q is also produced by extravillous trophoblast and is used to favor trophoblast migration through the decidua. Defective expression of C1q by trophoblast is associated with impaired trophoblast invasion of decidua and may have important implications in pregnancy disorders such as preeclampsia characterized by reduced vascular remodeling.

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“…These include several proteins from inflammatory pathways: HPX, complement factor H (CFH), C1R, cystatin 3 (CST3), APOA4 and AZGP1. In contrast to HNF1A, CFH and C1R do not respond to high levels of IL6 but react to other cytokines such as interferongamma (Goldberg et al 2007). This suggests that part of the SVD signals may be independent from and/or complementary to the HNF1A network.…”

Section: Spontaneous Labour and Vaginal Deliverymentioning

confidence: 99%

“…This suggests that part of the SVD signals may be independent from and/or complementary to the HNF1A network. Furthermore, high levels of CFH in SVD could cause the inhibition of both the classical and alternative pathways of complement activation, which emphasizes that a balance in inflammatory pathways must be maintained during human parturition (Whaley & Ruddy 1976, DiScipio 1981, 1992, Goldberg et al 2007. Several proteins associated with TNF were found to change in maternal peripheral plasma with labour.…”

Section: Spontaneous Labour and Vaginal Deliverymentioning

confidence: 99%

Low abundance plasma proteins in labour

Wang¹,

Heesom²,

Phillips³

et al. 2012

Reproduction

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Every year, millions of births worldwide are complicated by prematurity or difficult post-term deliveries, resulting in a high incidence of perinatal mortality and morbidity. Our poor understanding of human parturition is a key reason for our inability to improve the management of preterm and post-term birth. In this study, we used proteomic techniques to look into protein changes in placental blood plasma obtained from women before or after spontaneous or induced labour, with vaginal or caesarean section deliveries. Our aim was to understand the basic mechanisms of human parturition regardless of whether the signals that trigger labour are of maternal and/or fetal origin. We found proteins from 33 genes with significantly altered expression profiles in relation to mode of labour and delivery. Most changes in labour occurred in proteins associated with 'immune and defence responses'. Although the signal transduction and regulation of these pathways varied among modes of delivery, hepatocyte nuclear factor 1 homeobox A emerged as a shared protein in the mechanism of labour. Moreover, several apolipoproteins such as apolipoprotein A-IV and APOE were found to change with labour, and these changes were also confirmed in maternal plasma. This study has identified significant protein changes in placental intervillous plasma with labour and has revealed several pathways related to human parturition.

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Synthesis of complement proteins in the human chorion is differentially regulated by cytokines

Cited by 20 publications

References 20 publications

Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations

Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations

The Complement System at the Embryo Implantation Site: Friend or Foe?

Low abundance plasma proteins in labour

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