Tamm-Horsfall glycoprotein binds IgG with high affinity

Rhodes, Diana C. J.; Hinsman, E. J.; Rhodes, James A.

doi:10.1038/ki.1993.343

Cited by 45 publications

(31 citation statements)

References 49 publications

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“…These antibodies usually are of very low affinity [47] . Immunoglobulins also bind in an unspecific way to carbohydrates of uromodulin [48] . Therefore, it is likely that the described antiuromodulin antibodies in humans are not specific and are most likely an artifact.…”

Section: Uromodulin and Ckdmentioning

confidence: 99%

Uromodulin and Chronic Kidney Disease

Lhotta¹

2010

Kidney Blood Press Res

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Uromodulin (Tamm-Horsfall protein) is produced in the kidney by cells of the thick ascending limb and distal tubule. Recent genetic studies suggest a role of uromodulin in chronic kidney disease. Mutations in the UMOD gene cause uromodulin storage disease. They code for amino acid substitutions that lead to misfolding of the molecule and its retention in the endoplasmic reticulum. Single nucleotide polymorphisms in the region of the UMOD gene have been shown to be associated with chronic kidney disease and reduced glomerular filtration rate. These polymorphisms affect uromodulin concentration in the urine, and lower genetically determined urinary uromodulin concentrations seem to protect against renal disease. Chronic kidney disease is associated with higher serum levels of uromodulin. From animal experiments and human studies it is hypothesized that uromodulin entering the renal interstitium either by basolateral secretion or urinary back-leakage in damaged tubuli interacts with and stimulates cells of the immune system and thereby causes inflammation and progression of chronic kidney disease.

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Section: Uromodulin and Ckdmentioning

confidence: 99%

Uromodulin and Chronic Kidney Disease

Lhotta¹

2010

Kidney Blood Press Res

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“…A number of studies have suggested that UMOD plays a role in inflammation processes and modulation of immune system responses [3,[58][59][60][61][62][63][150][151][152][153][154][155][156][157][158][159] . This notion, however, comes mostly from in vitro studies or in vivo studies performed under artificial conditions, and their relevance for physiology and particularly for pathophysiology is debatable.…”

Section: Umod In Inflammation and Immunitymentioning

confidence: 99%

Uromodulin Biology and Pathophysiology – An Update

Vyleťal

Bleyer

Kmoch

2010

Kidney Blood Press Res

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Uromodulin (UMOD) is a glycoprotein expressed on the luminal surface of the apical membrane of renal tubular epithelial cells forming the thick ascending limb of Henle. Here, UMOD forms filamentous structures probably ensuring water impermeability and the countercurrent gradient. The multidomain structure, cellular topology of UMOD and clinical consequences associated with UMOD dysfunction, however, suggest that it may be involved in other biological processes such as receptor-mediated endocytosis, mechanosensation of urinary flow, Wnt-signaling, cell cycle regulation and planar cell polarity. A specific, but as yet unidentified, protease(s) releases UMOD into the urine, where it probably contributes to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and modulates formation of supersaturated salts and their crystals. UMOD expression, biosynthesis and excretion are regulated in a complex manner, and dysregulation is found in a wide range of pathological conditions. It is strongly reduced or absent in cases with mutations in UMOD, renin, HNF1B and other genetic disorders causing autosomal dominant hyperuricemic nephropathy. In contrast, elevated UMOD excretion may be associated with, and thus predictive of, chronic kidney disease. UMOD analysis is therefore of importance in all conditions with renal involvement and may be useful in the proper classification of renal diseases.

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“…Specifically, uromodulin has been shown to induce pro-inflammatory cytokine release from human whole blood [8], to activate myeloid dendritic cells (DC) to acquire a fully mature DC phenotype [9], and to activate monocytes [8]. Precisely how uromodulin orchestrates these diverse immunological properties is unknown, however the protein has been shown to bind with high affinity to a number of immuno-proteins including the complement factors C1, C1q and C3 [10,11], IgG [12,13] and cytokines such as TNF alpha, IL-1 beta and IL-8 [14]. It is thought that these diverse but potent pro-inflammatory properties of uromodulin may signal tubular damage and repair [8,9].…”

Section: Introductionmentioning

confidence: 99%

Uromodulin Facilitates Neutrophil Migration Across Renal Epithelial Monolayers

Schmid

Prajczer

Grüber

et al. 2010

Cell Physiol Biochem

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The glycosylated protein uromodulin is exclusively found in the thick ascending limb cells (TAL) of the kidney, where it is produced on mass and apically targeted, eventually being secreted into the urine. Recently, there has been a renewed interest in this protein due to its ability to interact with the immune system, implicating this protein as a renal inflammatory molecule. Here we investigated the potential role of membrane bound uromodulin on neutrophil adhesion and trans-epithelial migration. The renal tubular epithelial cell line, LLC-PK1, stably transfected with human uromodulin was used to investigate the influence of uromodulin on neutrophil adherence and migration. Uromodulin expression resulted in a significant increase of neutrophil adherence and trans-epithelial migration, in both the apical to basolateral and the basolateral to apical direction. Although uromodulin is GPI anchored and targeted to the apical membrane, we could also observe expression in the basal and lateral membranes domains, which may be responsible for basolateral to apical migration. Furthermore we show that uromodulin binds both the heavy and light chain of IgG, and that IgG enhances neutrophil migration. This study demonstrates that uromodulin can facilitate neutrophil trans-epithelial migration and that this migration can be amplified by co-factors such as IgG.

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Tamm-Horsfall glycoprotein binds IgG with high affinity

Cited by 45 publications

References 49 publications

Uromodulin and Chronic Kidney Disease

Uromodulin and Chronic Kidney Disease

Uromodulin Biology and Pathophysiology – An Update

Uromodulin Facilitates Neutrophil Migration Across Renal Epithelial Monolayers

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