The role of the liver in Catabolism of Mouse and Human IgA

Městecký, Jiří; Moldoveanu, Zina; Tomana, Milan; Epps, John; Thorpe, Suzanne R.; Phillips, John O.; Kulhavy, Rose

doi:10.3109/08820138909112245

Cited by 20 publications

(7 citation statements)

References 13 publications

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“…In humans and other animals, the i.v. injected IgA is also taken up and catabolized by hepatocytes rather than by nonparenchymal cells in the liver [30]. Egg lecithin-coated silicon particles injected into the portal vein are more actively phagocytosed by hepatocytes than by stellate macrophages in rats [24,42].…”

Section: Epithelial Apoptosis and Absorption Of Antigen And Its Specimentioning

confidence: 99%

Persorption of Luminal Antigenic Molecule and Its Specific Antibody via Apoptotic Epithelial Cells of Intestinal Villi and Peyer's Patches into Peripheral Blood in Rats

Yuji

Tsubata

Chin

et al. 2006

The Journal of Veterinary Medical Science

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ABSTRACT. The possibility of persorption of bovine serum albumin (BSA) molecules from mucous epithelial cells and its mechanism were investigated in rats orally pre-immunized by BSA for 14 consecutive days. In the small and large intestines, both the BSA antigen (BSAAg) and its specific antibody (SpAb) were absorbed by the epithelial cells at the late apoptotic stage (ApoEp), and were subsequently transcytosed by membranes of the small vesicles. The basal cytoplasms containing highly-concentrated BSA-Ag and SpAb were occasionally fragmented into small cytoplasmic droplets that were secreted into the lamina propria. In Peyer's patches, both BSA-Ag and SpAb were more actively absorbed and transcytosed toward the dome area by the ApoEp of the dome apex than by the M cells. BSA-Ag and SpAb were finally persorbed into the portal blood and lymph, but were never secreted into the bile. They were also engulfed by macrophage-like cells in the villous lamina propria, mesenteric lymph node and spleen, and by hepatocytes in the liver. These findings suggest that sensitized soluble luminal antigens are taken up by ApoEp in the small intestine and are finally persorbed into the peripheral blood. The uptake of luminal antigen might be mediated by its luminal SpAb.

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Section: Epithelial Apoptosis and Absorption Of Antigen And Its Specimentioning

confidence: 99%

Persorption of Luminal Antigenic Molecule and Its Specific Antibody via Apoptotic Epithelial Cells of Intestinal Villi and Peyer's Patches into Peripheral Blood in Rats

Yuji

Tsubata

Chin

et al. 2006

The Journal of Veterinary Medical Science

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“…NeuAc residues in IgA1 HR O -glycans influence the affinity of IgA1 to some receptors. For example, binding of IgA1 to asialoglycoprotein receptor (ASGP-R) is reduced by sialylation of IgA1 [70]–[75]. It also has been suggested that enhanced sialylation of IgA1 extended its half-life in the circulation due to reduced clearance [1], [49], [51].…”

Section: Discussionmentioning

confidence: 99%

Enzymatic Sialylation of IgA1 O-Glycans: Implications for Studies of IgA Nephropathy

et al. 2014

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Patients with IgA nephropathy (IgAN) have elevated circulating levels of IgA1 with some O-glycans consisting of galactose (Gal)-deficient N-acetylgalactosamine (GalNAc) with or without N-acetylneuraminic acid (NeuAc). We have analyzed O-glycosylation heterogeneity of naturally asialo-IgA1 (Ale) myeloma protein that mimics Gal-deficient IgA1 (Gd-IgA1) of patients with IgAN, except that IgA1 O-glycans of IgAN patients are frequently sialylated. Specifically, serum IgA1 of healthy controls has more α2,3-sialylated O-glycans (NeuAc attached to Gal) than α2,6-sialylated O-glycans (NeuAc attached to GalNAc). As IgA1-producing cells from IgAN patients have an increased activity of α2,6-sialyltransferase (ST6GalNAc), we hypothesize that such activity may promote premature sialylation of GalNAc and, thus, production of Gd-IgA1, as sialylation of GalNAc prevents subsequent Gal attachment. Distribution of NeuAc in IgA1 O-glycans may play an important role in the pathogenesis of IgAN. To better understand biological functions of NeuAc in IgA1, we established protocols for enzymatic sialylation leading to α2,3- or α2,6-sialylation of IgA1 O-glycans. Sialylation of Gal-deficient asialo-IgA1 (Ale) myeloma protein by an ST6GalNAc enzyme generated sialylated IgA1 that mimics the Gal-deficient IgA1 glycoforms in patients with IgAN, characterized by α2,6-sialylated Gal-deficient GalNAc. In contrast, sialylation of the same myeloma protein by an α2,3-sialyltransferase yielded IgA1 typical for healthy controls, characterized by α2,3-sialylated Gal. The GalNAc-specific lectin from Helix aspersa (HAA) is used to measure levels of Gd-IgA1. We assessed HAA binding to IgA1 sialylated at Gal or GalNAc. As expected, α2,6-sialylation of IgA1 markedly decreased reactivity with HAA. Notably, α2,3-sialylation also decreased reactivity with HAA. Neuraminidase treatment recovered the original HAA reactivity in both instances. These results suggest that binding of a GalNAc-specific lectin is modulated by sialylation of GalNAc as well as Gal in the clustered IgA1 O-glycans. Thus, enzymatic sialylation offers a useful model to test the role of NeuAc in reactivities of the clustered O-glycans with lectins.

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“…For example, purified asialoglycoprotein receptor (ASGP-R) from rat liver was shown to bind IgA (predominantly monomeric) from normal human serum (Stockert et al, 1982). In mice, uptake of mIgA by hepatic ASGP-R was shown to account for more catabolism of mIgA than all other tissues combined (Mestecky et al, 1989). Several lines of evidence suggest that the ASGP-R recognition sites on IgA are the O-linked oligosaccharides in the hinge region of the IgA1 subclass.…”

Section: Hepatic Uptake and Clearance Of Iga And Iga Icmentioning

confidence: 97%