Placental Expression of α2,6-Linked Sialic Acid is Upregulated in Malaria

Jones, Carolyn J.P.; Owens, Stephen; Senga, Edward; Rheenen, Patrick van; Faragher, Brian; Denton, J.; Brabin, Bernard

doi:10.1016/j.placenta.2007.12.007

Cited by 4 publications

(3 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, other data implicate additional terminal saccharides in initial adhesion. Glycans containing alpha 2-6-linked sialic acid are expressed at high levels on the STB microvillous surface of malaria-infected placentas [78] where they could facilitate the first steps of infection. In this regard, we detected iRBC binding to an alpha 2-6-containing saccharide on the glycan array.…”

Section: Discussionmentioning

confidence: 99%

Histopathologies, Immunolocalization, and a Glycan Binding Screen Provide Insights into Plasmodium falciparum Interactions with the Human Placenta

Hromatka¹,

Ngeleza²,

Adibi³

et al. 2013

Biology of Reproduction

View full text Add to dashboard Cite

During pregnancy, Plasmodium falciparum-infected erythrocytes cytoadhere to the placenta. Infection is likely initiated at two sites where placental trophoblasts contact maternal blood: 1) via syncytiotrophoblast (STB), a multicellular transporting and biosynthetic layer that forms the surface of chorionic villi and lines the intervillous space, and 2) through invasive cytotrophoblasts, which line uterine vessels that divert blood to the placenta. Here, we investigated mechanisms of infected erythrocyte sequestration in relationship to the microanatomy of the maternal-fetal interface. Histological analyses revealed STB denudation in placental malaria, which brought the stromal cores of villi in direct contact with maternal blood. STB denudation was associated with hemozoin deposition (P = 0.01) and leukocyte infiltration (P = 0.001) and appeared to be a feature of chronic placental malaria. Immunolocalization of infected red blood cell receptors (CD36, ICAM1/CD54, and chondroitin sulfate A) in placentas from uncomplicated pregnancies showed that STB did not stain, while the underlying villous stroma was immunopositive. Invasive cytotrophoblasts expressed ICAM1. In malaria, STB denudation exposed CD36 and chondroitin sulfate A in the villous cores to maternal blood, and STB expressed ICAM1. Finally, we investigated infected erythrocyte adherence to novel receptors by screening an array of 377 glycans. Infected erythrocytes bound Lewis antigens that immunolocalized to STB. Our results suggest that P. falciparum interactions with STB-associated Lewis antigens could initiate placental malaria. Subsequent pathologies, which expose CD36, ICAM1, and chondroitin sulfate A, might propagate the infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Histopathologies, Immunolocalization, and a Glycan Binding Screen Provide Insights into Plasmodium falciparum Interactions with the Human Placenta

Hromatka¹,

Ngeleza²,

Adibi³

et al. 2013

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…Protein stability is influenced by ROs ( 219 ). In placental malaria, increased chorionic villi α2,6 sialylation may influence intervillous placental parasite density as a compensatory response to Plasmodium falciparum infection ( 220 ). Preeclampsia and placental malaria are diseases with a placental and systemic inflammatory response in which NK cell activity increases progressively throughout gestation and may affect the communication between syncytiotrophoblast and immune cells ( 123 , 221 – 223 ).…”

Section: Introductionmentioning

confidence: 99%

Expression of placental glycans and its role in regulating peripheral blood NK cells during preeclampsia: a perspective

et al. 2023

View full text Add to dashboard Cite

Preeclampsia is a pregnancy-related multisystem disorder characterized by altered trophoblast invasion, oxidative stress, exacerbation of systemic inflammatory response, and endothelial damage. The pathogenesis includes hypertension and mild-to-severe microangiopathy in the kidney, liver, placenta, and brain. The main mechanisms involved in its pathogenesis have been proposed to limit trophoblast invasion and increase the release of extracellular vesicles from the syncytiotrophoblast into the maternal circulation, exacerbating the systemic inflammatory response. The placenta expresses glycans as part of its development and maternal immune tolerance during gestation. The expression profile of glycans at the maternal–fetal interface may play a fundamental role in physiological pregnancy changes and disorders such as preeclampsia. It is unclear whether glycans and their lectin-like receptors are involved in the mechanisms of maternal–fetal recognition by immune cells during pregnancy homeostasis. The expression profile of glycans appears to be altered in hypertensive disorders of pregnancy, which could lead to alterations in the placental microenvironment and vascular endothelium in pregnancy conditions such as preeclampsia. Glycans with immunomodulatory properties at the maternal–fetal interface are altered in early-onset severe preeclampsia, implying that innate immune system components, such as NK cells, exacerbate the systemic inflammatory response observed in preeclampsia. In this article, we discuss the evidence for the role of glycans in gestational physiology and the perspective of glycobiology on the pathophysiology of hypertensive disorders in gestation.

show abstract

“…The biological significance of α(2-6)-linked NeuAc is seen in work, which has demonstrated it to be important in renal function [47], be a marker for aggressive malignancy in colorectal carcinoma [48,49] undergo changes in expression in oral carcinogenesis [50] and have an involvement in malaria [51]. However, its role in the KS chains of articular cartilage fibromodulin is not clear.…”

Section: Introductionmentioning

confidence: 99%

Lectin affinity chromatography of articular cartilage fibromodulin: Some molecules have keratan sulphate chains exclusively capped by α(2-3)-linked sialic acid

2011

View full text Add to dashboard Cite

Fibromodulin from bovine articular cartilage has been subjected to lectin affinity chromatography by Sambucus nigra lectin which binds α(2-6)- linked N-acetylneuraminic acid, and the structure of the keratan sulphate in the binding and non-binding fractions examined by keratanase II digestion and subsequent high pH anion exchange chromatography. It has been confirmed that the keratan sulphate chains attached to fibromodulin isolated from bovine articular cartilage may have the chain terminating N-acetylneuraminic acid residue α(2-3)- or α(2-6)-linked to the adjacent galactose residue. Although the abundance of α(2-6)-linked N-acetylneuraminic acid (ca. 22%) is such that this could cap one of the four chains in almost all fibromodulin molecules, it was found that ca. 34% of the fibromodulin proteoglycan molecules from bovine articular cartilage were capped exclusively with α(2-3)-linked N-acetylneuraminic acid. The remainder of the fibromodulin proteoglycans, which bound to the lectin had a mixture of α(2-3)- and α(2-6)-linked N-acetylneuraminic acid capping structures. The keratan sulphates attached to fibromodulin molecules capped exclusively with α(2-3)- linked N-acetylneuraminic acid were found to have a higher level of galactose sulphation than those from fibromodulin with both α(2-3)- and α(2-6)-linked N-acetylneuraminic acid caps, which bound to the Sambucus nigra lectin. In addition, both pools contained chains of similar length (ca. 8-9 disaccharides). Both also contained α(1-3)-linked fucose, showing that this feature does not co-distribute with α(2-6)-linked N-acetylneuraminic acid, although these two features are present only in mature articular cartilage. These data show that there are discrete populations of fibromodulin within articular cartilage, which may have differing impacts upon tissue processes.

show abstract

Placental Expression of α2,6-Linked Sialic Acid is Upregulated in Malaria

Cited by 4 publications

References 31 publications

Histopathologies, Immunolocalization, and a Glycan Binding Screen Provide Insights into Plasmodium falciparum Interactions with the Human Placenta

Histopathologies, Immunolocalization, and a Glycan Binding Screen Provide Insights into Plasmodium falciparum Interactions with the Human Placenta

Expression of placental glycans and its role in regulating peripheral blood NK cells during preeclampsia: a perspective

Lectin affinity chromatography of articular cartilage fibromodulin: Some molecules have keratan sulphate chains exclusively capped by α(2-3)-linked sialic acid

Contact Info

Product

Resources

About