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The Turkish Journal of Gastroenterology... Feb 2022Glycosylation is a common post-translational modification, and it has been reported that alterations in the glycosylation patterns on cells are related to cell...
BACKGROUND
Glycosylation is a common post-translational modification, and it has been reported that alterations in the glycosylation patterns on cells are related to cell proliferation, differentiation, tissue adhesion, and carcinogenesis. This study aimed to investigate the relationship between Helicobacter pylori infection and gastric mucosal glycosylation using a lectin microarray system.
METHODS
Gastric mucosal samples were obtained from 10 Helicobacter pylori-non-infected patients, 10 H. pylori-infected patients, and 10 after H. pylori-eradicated patients who underwent gastric mucosal biopsy by endoscopy in our institute. The gastric gland cells which were isolated from formalin-fixed, paraffin-embedded gastric mucosal biopsy samples using laser capture microdissection were used for lectin microarray to obtain lectin-glycan interaction values.
RESULTS
Comparison of the lectin-glycan interaction values before and after eradication in the same patients showed significant increases for Ricinus communis agglutinin 120, Trichosanthes japonica agglutinin II, Euonymus europaeus lectin, jacalin, Amaranthus caudatus agglutinin, and Maclura pomifera agglutinin and significant decreases for Urtica dioica agglutinin, Lycopersicon esculentum lectin, Ulex europaeus agglutinin, Sambucus nigra agglutinin, Sambucus sieboldiana agglutinin, and Trichosanthes japonica agglutinin I. Furthermore, jacalin and MPA in the gastric antrum were significantly decreased with H. pylori infection compared with the without infection group and improved to the levels seen without infection as a result of eradication. Lycopersicon esculentum lectin, Sambucus nigra agglutinin, Sambucus sieboldiana agglutinin, and Trichosanthes japonica agglutinin I in the gastric body were significantly increased with H. pylori infection and improved to the level seen without infection as a result of eradication.
CONCLUSION
H. pylori infection changes the lectin binding state which is related to various cancers on the gastric mucosal cell. Furthermore, those changes are reversible by H. pylori eradication.
Topics: Agglutinins; Gastric Mucosa; Glycosylation; Helicobacter Infections; Helicobacter pylori; Humans; Lectins; Microarray Analysis; Polysaccharides
PubMed: 35238778
DOI: 10.5152/tjg.2021.201116 -
Proceedings of the National Academy of... Sep 2023SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular...
SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety of biophysical approaches, we demonstrate that the interaction is avidity driven and that BOA cross-links the spike protein into soluble aggregates. Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that multivalent glycan-targeting molecules have the potential to act as pan-coronavirus inhibitors.
Topics: Humans; COVID-19; RNA, Viral; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virus Internalization; Agglutinins; Lectins; Polysaccharides
PubMed: 37695910
DOI: 10.1073/pnas.2301518120 -
PloS One 2016Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. The etiology is not clear, but an immune attack towards components of...
Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. The etiology is not clear, but an immune attack towards components of placenta or fetus has been indicated. This involves activation of the complement system in the placenta. We have previously described the presence of the complement-regulating protein salivary scavenger and agglutinin (SALSA) in amniotic fluid. In this study we investigated the potential role of SALSA in pregnancy by analyzing its presence in amniotic fluid and placental tissue during healthy and complicated pregnancies. SALSA levels in amniotic fluid increased during pregnancy. Before 20 weeks of gestation the levels were slightly higher in patients who later developed pre-eclampsia than in gestation age-matched controls. In the placenta of pre-eclamptic patients syncytial damage is often followed by the formation of fibrinoid structures. SALSA was found clustered into these fibrinoid structures in partial co-localization with complement C1q and fibronectin. In vitro analysis showed direct protein binding of SALSA to fibronectin. SALSA binds also to fibrin/fibrinogen but did not interfere with the blood clotting process in vitro. Thus, in addition to antimicrobial defense and epithelial differentiation, the data presented here suggest that SALSA, together with fibronectin and C1q, may be involved in the containment of injured placental structures into fibrinoids.
Topics: Agglutinins; Amniotic Fluid; Blood Coagulation; Calcium-Binding Proteins; Complement C1q; DNA-Binding Proteins; Female; Fibronectins; Fluorescent Antibody Technique; Humans; Placenta; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Receptors, Cell Surface; Saliva; Tumor Suppressor Proteins
PubMed: 26828433
DOI: 10.1371/journal.pone.0147867 -
Microbiological Reviews Mar 1992The sexual agglutinins of the budding yeasts are cell adhesion proteins that promote aggregation of cells during mating. In each yeast species, complementary agglutinins... (Comparative Study)
Comparative Study Review
The sexual agglutinins of the budding yeasts are cell adhesion proteins that promote aggregation of cells during mating. In each yeast species, complementary agglutinins are expressed by cells of opposite mating type that interact to mediate aggregation. Saccharomyces cerevisiae alpha-agglutinin and its analogs from other yeasts are single-subunit glycoproteins that contain N-linked and O-linked oligosaccharides. The N-glycosidase-sensitive carbohydrate is not necessary for activity. The proposed binding domain of alpha-agglutinin has features characteristic of the immunoglobulin fold structures of cell adhesion proteins of higher eukaryotes. The C-terminal region of alpha-agglutinin plays a role in anchoring the glycoprotein to the cell surface. The S. cerevisiae alpha-agglutinin and its analogs from other species contain multiple subunits; one or more binding subunits, which interact with the opposite agglutinin, are disulfide bonded to a core subunit, which mediates cell wall anchorage. The core subunits are composed of 80 to 95% O-linked carbohydrate. The binding subunits have less carbohydrate, and both carbohydrate and peptide play roles in binding. The alpha-agglutinin and alpha-agglutinin genes from S. cerevisiae have been cloned and shown to be regulated by the mating-type locus, MAT, and by pheromone induction. The agglutinins are necessary for mating under conditions that do not promote cell-cell contact. The role of the agglutinins therefore is to promote close interactions between cells of opposite mating type and possibly to facilitate the response to phermone, thus increasing the efficiency of mating. We speculate that they mediate enhanced response to sex pheromones by providing a synapse at the point of cell-cell contact, at which both pheromone secretion and cell fusion occur.
Topics: Agglutinins; Cell Adhesion Molecules; Conjugation, Genetic; Glycoproteins; Mating Factor; Peptides; Pheromones; Yeasts
PubMed: 1579109
DOI: 10.1128/mr.56.1.180-194.1992 -
Infection and Immunity Feb 1987Previous studies have suggested that both secretory immunoglobulin A (sIgA) and various nonimmunoglobulin salivary glycoproteins are capable of agglutinating a variety...
Previous studies have suggested that both secretory immunoglobulin A (sIgA) and various nonimmunoglobulin salivary glycoproteins are capable of agglutinating a variety of bacteria. The present study was designed to compare the nature of the agglutinins for Streptococcus mutans and Salmonella typhimurium in parotid saliva and colostrum. S. mutans was aggregated by saliva and colostrum, whereas S. typhimurium was aggregated only by saliva as detected by a spectrophotometric method. The principal salivary agglutinin for both S. mutans and S. typhimurium was calcium dependent and could be desorbed in phosphate-buffered saline (pH 6.8). In contrast, the colostral agglutinin was calcium independent and not readily desorbed. The agglutinin activities of saliva and colostrum for S. mutans were additive, suggesting independent target sites on the bacterial surface. The agglutinin activity of colostrum was totally associated with sIgA as was suggested by blocking of the agglutinating activity with anti-alpha-chain serum and the absence of blocking with an antibody specific for salivary agglutinin. Interestingly, anti-alpha-chain serum removed all agglutinating activity from saliva, but not from the phosphate-buffered saline-desorbed agglutinin. Dialysis of parotid saliva against 0.1 M disodium EDTA eliminated the agglutinin blocking activity of anti-alpha-chain serum but not that of the antiagglutinin antibody. The ability of anti-alpha-chain serum to block agglutination of the EDTA-dialyzed saliva could be restored by the addition of calcium chloride, suggesting that sIgA and salivary agglutinin are associated through a calcium-mediated interaction. These results indicate that bacterial agglutinating activity of colostrum, as detected spectrophotometrically, is mediated by sIgA, and that of saliva is mainly dependent upon a calcium-dependent nonimmunoglobulin agglutinin. The agglutinating activities of sIgA and parotid agglutinin seem to be additive, and their calcium-dependent association may favor the enhancement of their respective activities.
Topics: Agglutination; Agglutinins; Bacteria; Calcium; Colostrum; Edetic Acid; Immunoglobulin A, Secretory; Saliva; Salmonella typhimurium; Streptococcus mutans
PubMed: 3100447
DOI: 10.1128/iai.55.2.288-292.1987 -
Tissue & Cell Jun 2023Recent investigations suggest the potential negative impact of SARS-CoV-2 infection on pregnant women and pregnancy outcome. In addition, some studies have described...
INTRODUCTION
Recent investigations suggest the potential negative impact of SARS-CoV-2 infection on pregnant women and pregnancy outcome. In addition, some studies have described pathological changes in the placental tissue of SARS-CoV-2-positive mothers, which are related or not to the infection severity and/or infection trimester. Among the various molecules involved in the normal structure and functionality of the placenta, sialic acids (Sias) seem to play an important role. Hence, we aimed to investigate possible changes in the distribution and content of Sias with different glycosidic linkages, namely α2,3 and α2,6 Galactose- or N-acetyl-Galactosamine-linked Sias and polymeric Sia (PolySia), in placentas from pregnant women infected by SARS-CoV-2 during the three different pregnancy trimesters.
METHODS
α2,3 and α2,6 Galactose-linked Sias were evaluated by lectin histochemistry (Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA), respectively), while immunohistochemistry was used for PolySia detection.
RESULTS
Data showed lower levels of α2,3 Galactose-linked Sias in the trophoblast and underlying basement membrane/basal plasma membrane in placentas from women infected during the second and third infection trimester compared with uninfected cases and those infected during first trimester. On the other hand, higher levels of PolySia were detected in the trophoblast during the second and third infection trimester.
CONCLUSIONS
Our findings suggest that changes in the sialylation status of trophoblast and its basement membrane/basal plasma membrane, together with other concomitant factors, could be at the basis of the most common placental histopathological alterations and gestational complications found especially in pregnancies with SARS-CoV-2 infection during the second and third trimester.
Topics: Pregnancy; Female; Humans; Placenta; COVID-19; SARS-CoV-2; Galactose; Agglutinins
PubMed: 36948081
DOI: 10.1016/j.tice.2023.102074 -
Nature Communications May 2022Candida albicans is the most common fungal pathogen and a prevalent cause of deadly bloodstream infections. Better understanding of the immune response against it, and...
Candida albicans is the most common fungal pathogen and a prevalent cause of deadly bloodstream infections. Better understanding of the immune response against it, and the ways by which it evades immunity, are crucial for developing new therapeutics against it. Natural Killer (NK) cells are innate lymphocytes best known for their role against viruses and tumors. In recent years it became clear that NK cells also play an important role in anti-fungal immunity. Here we show that while NK cells recognize and eliminate C. albicans, the fungal cells inhibit NK cells by manipulating the immune checkpoint receptor TIGIT (T cell immunoreceptor with Ig and ITIM domains) in both humans and mice. We identify the responsible fungal ligands as members of the Als (Agglutinin-Like Sequences) protein family. Furthermore, we show that blocking this interaction using immunotherapy with a TIGIT-blocking antibody can re-establish anti-Candida immunity and serve as a potential therapeutic tool.
Topics: Agglutinins; Animals; Candida albicans; Immunotherapy; Killer Cells, Natural; Mice; Receptors, Immunologic
PubMed: 35513379
DOI: 10.1038/s41467-022-30087-z -
International Journal of Biological... Jun 2020Lectins are ubiquitous carbohydrate-binding proteins that interact with sugar moieties in a highly specific manner. H-type lectins represent a new group of lectins that... (Review)
Review
Lectins are ubiquitous carbohydrate-binding proteins that interact with sugar moieties in a highly specific manner. H-type lectins represent a new group of lectins that were identified in invertebrates. These lectins share structural homology and bind mainly to N-acetylgalactosamine (GalNAc). Recent structural studies on the H-type lectins provided a detailed description of the GalNAc-lectin interaction that is already exploited in a number of biomedical applications. Two members of the H-type lectin family, Helix pomatia agglutinin (HPA) and Helix aspersa agglutinin (HAA), have already been extensively used in many diagnostic tests due their ability to specifically recognize GalNAc. This ability is especially important because aberrant glycosylation patterns of proteins expressed by cancer cells contain GalNAc. In addition, H-type lectins were utilized in diagnostics of other non-cancer diseases and represent great potential as components of drug delivery systems. Here, we present an overview of the H-type lectins and their applications in diagnostics, analytics and drug delivery.
Topics: Acetylgalactosamine; Agglutinins; Amino Acid Sequence; Animals; Drug Delivery Systems; Glycosylation; Humans; Lectins; Plant Lectins
PubMed: 32119947
DOI: 10.1016/j.ijbiomac.2020.02.320 -
The Journal of Cell Biology Sep 1985Using the quick-freeze, deep-etch technique, we compare the structure of the cane-shaped plus and minus sexual agglutinin molecules purified from gametes of...
Using the quick-freeze, deep-etch technique, we compare the structure of the cane-shaped plus and minus sexual agglutinin molecules purified from gametes of Chlamydomonas reinhardi. We also describe the structure of three additional gamete-specific fibrillar molecules, called short canes, loops, and crescents, which are structurally related to the agglutinins. Four non-agglutinating mutant strains are found to produce the three latter fibrils but not canes, supporting our identification of the cane-shaped molecule as the agglutinin. The heads of the plus and minus canes are shown to differ in morphology. Moreover, two treatments that inactivate the plus agglutinin in vitro--thermolysin digestion and disulfide reduction/alkylation--bring about detectable structural changes only in the head domain of the cane, suggesting that the head may play an indispensible role in affecting gametic recognition/adhesion. We also present quick-freeze, deep-etch images of the flagellar surfaces of gametic, vegetative, and mutant cells of Chlamydomonas reinhardi. The gametic flagella are shown to carry the canes, short canes, loops, and crescents present in in vitro preparations. The cane and crescent proteins self-associate on the flagellar surface into stout fibers of uniform caliber, and they align along the longitudinal axis of the flagellum. The short canes and loops co-purify with flagella but, in the presence of mica, dissociate so that they lie to the sides of the flagella. The agglutinin canes of both mating types are oriented with their hooks at the membrane surface and their heads directed outward, where they are positioned to participate in the initial events of sexual agglutination.
Topics: Agglutinins; Alkylation; Cell Aggregation; Cell Membrane; Chlamydomonas; Flagella; Freeze Etching; Membrane Proteins; Mutation; Oxidation-Reduction; Protein Conformation; Thermolysin
PubMed: 4030899
DOI: 10.1083/jcb.101.3.924 -
Clinical Oral Investigations Jan 2024Crohn's disease patients, who are prone to develop periodontal diseases, may carry genetic defects in their Th17 cytokine, human beta-defensin (hBD) 1-3, and salivary...
OBJECTIVES
Crohn's disease patients, who are prone to develop periodontal diseases, may carry genetic defects in their Th17 cytokine, human beta-defensin (hBD) 1-3, and salivary and scavenger agglutinin (SALSA) expressions. Biochemical composition of saliva reflects the oral consequences of systemic immune response modifications. Our aim was to evaluate the salivary Th17 cytokine, epithelial hBD 1-3, and SALSA levels in relation to Crohn's disease.
MATERIALS AND METHODS
This cross-sectional study included 42 Crohn's disease patients and 34 systemically healthy controls. Periodontal and dental indexes were measured, and stimulated saliva samples were collected. Salivary Th17 cytokine levels were analyzed by multiplex technique, and hBD 1-3 and SALSA levels by enzyme-linked immunosorbent assay.
RESULTS
There were 19 gingivitis and 11 initial periodontitis patients in the Crohn's disease group, and 15 gingivitis and 4 initial periodontitis in the control group. In comparison to controls, higher salivary Th17 cytokine levels were observed in Crohn's disease patients. No statistical difference was observed between Crohn's disease and control groups in terms of their salivary hBD 1-3 and SALSA levels. Based on the regression analysis, there is no independent association between Crohn's disease and salivary Th17 cytokine levels.
CONCLUSIONS
Crohn's disease does not relate to salivary antimicrobial hBD 1-3 or SALSA levels. While Crohn's disease patients have higher salivary Th17 cytokine levels in comparison to systemically healthy controls, an independent association between Crohn's disease and Th17 cytokine profile is still missing.
CLINICAL RELEVANCE
Diminished Th17 cytokine response in Crohn's disease, which might be related to genetic susceptibility, can be also visualized in saliva.
Topics: Humans; Agglutinins; beta-Defensins; Crohn Disease; Cross-Sectional Studies; Cytokines; Gingivitis; Periodontitis
PubMed: 38246944
DOI: 10.1007/s00784-024-05509-5