Abstract:Acute and chronic inflammation-induced expression of sialyl LewisX has already been shown to occur on alpha1-acid glycoprotein. We now demonstrate that this phenomenon is not restricted to alpha1-acid glycoprotein but also occurs on two other acute-phase proteins. ie on alpha1-antichymotrypsin and on haptoglobin. The level of expression of sialyl LewisX on these proteins was lower than on alpha1-acid glycoprotein, in all likelihood because alpha1-acid glycoprotein is the only acute-phase protein containing tet… Show more
“…These results are in agreement with the observations that inflammation, and particularly TNF-␣, changes ␣3-fucosylation and induces sialyl-Lewis x expression on several glycoproteins (23,51,52). ␣1,3-Fucosyltransferases are required after ␣2,3-sialyltransferases in the generation of the sialyl-Le x determinants.…”
Section: Fig 2 Hpaec Elution Profile Of Mixtures Containing Radiolasupporting
There is increasing evidence that inflammation may affect glycosylation and sulfation of various glycoproteins. The present study reports the effect of tumor necrosis factor ␣ (TNF-␣), a proinflammatory cytokine, on the glycosyl-and sulfotransferases of the human bronchial mucosa responsible for the biosynthesis of Lewis x epitope and of its sialylated and/or sulfated derivatives, which are expressed in human bronchial mucins. Fragments of macroscopically normal human bronchial mucosa were exposed to TNF-␣ at a concentration of 20 ng/ml. TNF-␣ was shown to increase ␣1,3-fucosyltransferase activity as well as expression of the two ␣1,3-fucosyltransferase genes expressed in the human airway, FUT3 and FUT4. It had no influence on ␣1,2-fucosyltransferase activity or FUT2 expression. It also increased ␣2,3-sialyltransferase activity and the expression of ST3Gal-III and, more importantly, ST3Gal-IV and both N-acetylglucosamine 6-O-sulfotransferase and galactose 3-O-sulfotransferase. These results are consistent with the observation of oversialylation and increased expression sialyl-Lewis x epitopes on human airway mucins secreted by patients with severe lung infection such as those with cystic fibrosis, whose airways are colonized by Pseudomonas aeruginosa. However, other cytokines may also be involved in this process.
“…These results are in agreement with the observations that inflammation, and particularly TNF-␣, changes ␣3-fucosylation and induces sialyl-Lewis x expression on several glycoproteins (23,51,52). ␣1,3-Fucosyltransferases are required after ␣2,3-sialyltransferases in the generation of the sialyl-Le x determinants.…”
Section: Fig 2 Hpaec Elution Profile Of Mixtures Containing Radiolasupporting
There is increasing evidence that inflammation may affect glycosylation and sulfation of various glycoproteins. The present study reports the effect of tumor necrosis factor ␣ (TNF-␣), a proinflammatory cytokine, on the glycosyl-and sulfotransferases of the human bronchial mucosa responsible for the biosynthesis of Lewis x epitope and of its sialylated and/or sulfated derivatives, which are expressed in human bronchial mucins. Fragments of macroscopically normal human bronchial mucosa were exposed to TNF-␣ at a concentration of 20 ng/ml. TNF-␣ was shown to increase ␣1,3-fucosyltransferase activity as well as expression of the two ␣1,3-fucosyltransferase genes expressed in the human airway, FUT3 and FUT4. It had no influence on ␣1,2-fucosyltransferase activity or FUT2 expression. It also increased ␣2,3-sialyltransferase activity and the expression of ST3Gal-III and, more importantly, ST3Gal-IV and both N-acetylglucosamine 6-O-sulfotransferase and galactose 3-O-sulfotransferase. These results are consistent with the observation of oversialylation and increased expression sialyl-Lewis x epitopes on human airway mucins secreted by patients with severe lung infection such as those with cystic fibrosis, whose airways are colonized by Pseudomonas aeruginosa. However, other cytokines may also be involved in this process.
“…The increase of the monofucosylated triantennary trisialylated N-glycan at m / z 3776.9, carrying a sialyl Lewis X antigen, that was reported here is a common feature in several cancers and inflammatory conditions: prostate metastatic cancer [43], lung cancer [44], breast cancer [27], acute pancreatitis, and sepsis [29]. The sialyl Lewis X antigen is carried by acute-phase glycoproteins that circulate in serum of patients suffering from inflammatory conditions: α -1 acid glycoprotein, haptoglobin, and α 1-antichymotrypsin [45]. In addition, the upregulation of the corresponding glycosyltransferases was also measured in the serum of ovarian cancer patients: ( α 1-3) fucosyltransferase [46], ( β 1-4) galactosyltransferase [47], and ( α 2-6) sialyltransferase [48, 49].…”
Epithelial ovarian cancer (EOC) is the sixth most common cause of cancer deaths in women because the diagnosis occurs mostly when the disease is in its late-stage. Current diagnostic methods of EOC show only a moderate sensitivity, especially at an early-stage of the disease; hence, novel biomarkers are needed to improve the diagnosis. We recently reported that serum glycome modifications observed in late-stage EOC patients by MALDI-TOF-MS could be combined as a glycan score named GLYCOV that was calculated from the relative areas of the 11 N-glycan structures that were significantly modulated. Here, we evaluated the ability of GLYCOV to recognize early-stage EOC in a cohort of 73 individuals comprised of 20 early-stage primary serous EOC, 20 benign ovarian diseases (BOD), and 33 age-matched healthy controls. GLYCOV was able to recognize stage I EOC whereas CA125 values were statistically significant only for stage II EOC patients. In addition, GLYCOV was more sensitive and specific compared to CA125 in distinguishing early-stage EOC from BOD patients, which is of high relevance to clinicians as it is difficult for them to diagnose malignancy prior to operation.
“…AGP fucosylation does not significantly change after one year of anti-inflammatory therapy, and it was hypothesized that the persistent high level of AGP-fucosylated residues may reflect a basic pathogenic inflammatory status that persists during the short-term of the clinically apparent disease activity [135]. Interestingly, this increase in fucosylation is not exclusive to AGP but has also been described for other acute phase proteins, including haptoglobin [136] and 1-antichimotrypsin [137]: in both proteins the majority of the (1 )3-linked fucose were present as sLe X conformation. AGP's glycan pattern modification has also been investigated in other autoimmune diseases.…”
Section: Glycan Pattern Modification Of Agp During Diseasementioning
Glycosylation is one of the most important post-translational modifications of proteins, and has been widely acknowledged as one of the most important ways to modulate both protein function and lifespan. The acute phase proteins are a major group of serum proteins whose concentration is altered during various pathophysiological conditions. The aim of this paper is to review the structure and functions of the alpha1-acid glycoprotein (AGP). AGP belongs to the subfamily of immunocalins, a group of binding proteins that also have immunomodulatory functions. One of the most interesting features of AGP is that its glycosylation microheterogeneity can be modified during diseases. This aspect is particularly remarkable, since both the immunomodulatory and the binding properties of AGP strongly depend on its carbohydrate composition. For these reasons, AGP can be considered an outstanding model for the study of glycan pattern modification during diseases. This review is focused on the most recent studies on the occurrence of different glycoforms in plasma and tissues and how the appearance of different oligosaccharide patterns during systemic inflammation or diseases can influence AGP's biological functions. The first part of the review will describe the structure of AGP and the several biological functions identified so far for this protein. The second part will be devoted to the post-translational modifications of the oligosaccharides micro-heterogeneity of AGP caused by pathological states. A critical evaluation of the impact of different AGP glycoforms on both its transport and anti-inflammatory features, and how the modifications of the glycan pattern can be utilized in clinical biochemistry, is also discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.