Erythrocytic membrane anionic charge, sialic acid content, and their correlations with urinary glycosaminoglycans in preeclampsia and eclampsia

Sen, Papia; Ghosh, Debdatta; Sarkar, Chandan

doi:10.1080/00365513.2020.1750687

Cited by 4 publications

(4 citation statements)

References 23 publications

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“…From a physical standpoint, the acidic functional groups of sialylated glycans confer a negative charge to the cell surface. Alterations in the organization and net charge contributed by sialic acids are understood to contribute to pathophysiologies of the blood and renal systems (93)(94)(95)(96)(97) and could likewise impair functions of the vaginal epithelium. In addition to physical effects, the liberation of sialic acids from host cell glycans can provide opportunities for bacterial nutrient acquisition and colonization, including some opportunistic pathogens lacking sialidase activity (62,(98)(99)(100).…”

Section: Discussionmentioning

confidence: 99%

Resident microbes shape the vaginal epithelial glycan landscape

Agarwal,

Choudhury,

Robinson

et al. 2023

Sci. Transl. Med.

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Epithelial cells are covered in carbohydrates (glycans). This glycan coat or “glycocalyx” interfaces directly with microbes, providing a protective barrier against potential pathogens. Bacterial vaginosis (BV) is a condition associated with adverse health outcomes in which bacteria reside in direct proximity to the vaginal epithelium. Some of these bacteria, including Gardnerella , produce glycosyl hydrolase enzymes. However, glycans of the human vaginal epithelial surface have not been studied in detail. Here, we elucidate key characteristics of the “normal” vaginal epithelial glycan landscape and analyze the impact of resident microbes on the surface glycocalyx. In human BV, glycocalyx staining was visibly diminished in electron micrographs compared to controls. Biochemical and mass spectrometric analysis showed that, compared to normal vaginal epithelial cells, BV cells were depleted of sialylated N - and O -glycans, with underlying galactose residues exposed on the surface. Treatment of primary epithelial cells from BV-negative women with recombinant Gardnerella sialidases generated BV-like glycan phenotypes. Exposure of cultured VK2 vaginal epithelial cells to recombinant Gardnerella sialidase led to desialylation of glycans and induction of pathways regulating cell death, differentiation, and inflammatory responses. These data provide evidence that vaginal epithelial cells exhibit an altered glycan landscape in BV and suggest that BV-associated glycosidic enzymes may lead to changes in epithelial gene transcription that promote cell turnover and regulate responses toward the resident microbiome.

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Section: Discussionmentioning

confidence: 99%

Resident microbes shape the vaginal epithelial glycan landscape

Agarwal,

Choudhury,

Robinson

et al. 2023

Sci. Transl. Med.

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“…From a physical standpoint, the acidic functional groups of sialylated glycans confer a negative charge to the cell surface. Alterations in the organization and net charge contributed by sialic acids are understood to contribute to pathophysiologies of the blood and renal systems [83][84][85][86][87] , and could likewise impair functions of the vaginal epithelium. In addition to physical effects, liberation of cellular sialic acids provides new opportunities for bacterial nutrient acquisition and colonization, including some opportunistic pathogens lacking sialidase activity 61,[88][89][90] .…”

Section: Discussionmentioning

confidence: 99%

Resident microbes shape the vaginal epithelial glycan landscape

Agarwal

Choudhury

Robinson

et al. 2022

Preprint

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Epithelial cells are covered in carbohydrates. This glycan coat or glycocalyx interfaces directly with microbes, providing a protective barrier against potential pathogens. Bacterial vaginosis is a condition associated with adverse health outcomes in which bacteria reside in direct proximity to the vaginal epithelium. Some of these bacteria, including Gardnerella, produce glycosyl hydrolase enzymes. However, glycans of the vaginal epithelial surface have not been studied in detail. Here we elucidate key characteristics of the vaginal epithelial glycan landscape and determine the impact of resident microbes on the surface glycocalyx. In BV, the glycocalyx was visibly diminished. We show that the normal vaginal epithelium displays sialylated N- and O-glycans by biochemical and mass spectrometric analysis. In contrast, BV-epithelial cell glycans were strikingly depleted of sialic acids, with underlying galactose residues exposed on the surface. Treatment of cells from BV-negative women with recombinant Gardnerella sialidases generated BV-like glycan characteristics. Together these data provide the first evidence that the vaginal epithelial glycocalyx is attacked by hydrolytic enzymes in BV. Given the widespread structural and functional roles of sialoglycans in biology and disease, these findings may point to a shared epithelial pathophysiology underlying the many adverse outcomes associated with BV.

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“…Increased RBC aggregation can be attributed to the reduced sialic acid content of the cell membrane that weakens repulsive forces [21] and conformational changes of the membrane enhancing erythrocyte aggregation [22]. A most recent study also confirmed decreased erythrocytic membrane anionic charge due to the reduced sialic acid content of the erythrocyte cell membrane in women with PE/eclampsia, which may be responsible for the aggregation of erythrocytes in these conditions [23].…”

Section: Rbc Aggregationmentioning

confidence: 94%

Peripartum Investigation of Red Blood Cell Properties in Women Diagnosed with Early-Onset Preeclampsia

Csiszar

Galos

Funke

et al. 2021

Cells

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We investigated peripartum maternal red blood cell (RBC) properties in early-onset preeclampsia (PE). Repeated blood samples were taken prospectively for hemorheological measurements at PE diagnosis (n = 13) or during 26–34 weeks of gestation in healthy pregnancies (n = 24), then at delivery, and 72 h postpartum. RBC aggregation was characterized by M index (infrared light transmission between the aggregated RBCs in stasis) and aggregation index (AI—laser backscattering from the RBC aggregates). We observed significantly elevated RBC aggregation (M index = 9.8 vs. 8.5; AI = 72.9% vs. 67.5%; p < 0.001) and reduced RBC deformability in PE (p < 0.05). A positive linear relationship was observed between AI and gestational age at birth in PE by regression analysis (R2 = 0.554; p = 0.006). ROC analysis of AI showed an AUC of 0.84 (0.68–0.99) (p = 0.001) for PE and indicated a cutoff of 69.4% (sensitivity = 83.3%; specificity = 62.5%), while M values showed an AUC of 0.75 (0.58–0.92) (p = 0.019) and indicated a cutoff of 8.39 (sensitivity = 90.9% and specificity = 50%). The predicted probabilities from the combination of AI and M variables showed increased AUC = 0.90 (0.79–1.00) (p < 0.001). Our results established impaired microcirculation in early-onset PE manifesting as deteriorated maternal RBC properties. The longer the pathologic pregnancy persists, the more pronounced the maternal erythrocyte aggregation. AI and M index could help in the prognostication of early-onset PE, but further investigations are warranted to confirm the prognostic role before the onset of symptoms.

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Erythrocytic membrane anionic charge, sialic acid content, and their correlations with urinary glycosaminoglycans in preeclampsia and eclampsia

Cited by 4 publications

References 23 publications

Resident microbes shape the vaginal epithelial glycan landscape

Resident microbes shape the vaginal epithelial glycan landscape

Resident microbes shape the vaginal epithelial glycan landscape

Peripartum Investigation of Red Blood Cell Properties in Women Diagnosed with Early-Onset Preeclampsia

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