Binding of dimeric and polymeric IgA to rat renal mesangial cells enhances the release of interleukin 6

Van Den Dobbelsteen, Marieke E. A.; Van Der Woude, Fokko J.; Schroeijers, Willeke E. M.; Van Den Wall Bake, A. Warmold L.; Van Es, Leenbert A.; Daha, Mohamed R.
August 1994
Kidney International;Aug1994, Vol. 46 Issue 2, p512
Academic Journal
The mesangium plays a crucial role in processes of inflammation in the kidney. Since deposits of IgA in the mesangium in patients with IgA nephropathy suggest a role for IgA in the inflammatory process, we investigated whether IgA is able to bind to cultured rat mesangial cells (MC) in vitro and induce activation of MC. As a source of IgA, monomeric (mIgA), dimeric (dIgA) and polymeric IgA-α-DNP (pIgA) rat monoclonal antibodies were used. FACS analysis indicated binding of dIgA and pIgA to MC while only a small percentage of the cells exhibited binding of mIgA. Additional experiments employing radiolabeled IgA revealed a time- and dose-dependent binding of 125IdIgA and 125I-pIgA with 6 · 106 binding sites for dIgA with an affinity of 5.5 · 106 M-1 and 7.2 · 106 binding sites/cell for pIgA with an affinity of 1.2 · 106 M-1. As compared to 125M-dlgA and 125I-pIgA, little binding of 125I-mIgA to MC occurred; the binding of dIgA and pIgA was not influenced by excess cold BSA, IgG or asialofeluin. Since some studies have suggested that fibronectin might interact with IgA, the binding of IgA to MC in the presence or absence of fibronectin or the RGD fragment was also analyzed. However no influence of fibronectin or the RGD fragment on binding of dIgA and pIgA to MC was observed. As a measure for activation of MC by IgA, the production of IL-6 by MC was analyzed. Dimeric IgA and pIgA both induced a dose-dependent increase of IL-6 production by MC. These studies suggest that especially dIgA and pIgA are potent activators of MC, while mIgA is relatively ineffective in this respect.


Related Articles

  • Deficient IgAl immune response to nasal cholera toxin subunit B in primary IgA nephropathy. de Fijter, Johan W.; Eijgenram, Jan W.; Braam, Carine A.; Holmgren, Jan; Daha, Mohamed R.; van Es, Leendert A.; van den Wall Bake, A. Warmold L. // Kidney International;Sep1996, Vol. 50 Issue 3, p952 

    Twelve IgA nephropathy (IgAN) patients and 18 controls were immunized with novel protein antigens, cholera toxin subunit B (CTB) via the nasal route and keyhole limpet hemocyanin (KLU) subcutaneously. Antibody secreting cells and antibody response in body fluids were determined by ELISPOT assay...

  • Complement membrane attack (MAC) in idiopathic IgA-glomerulonephritis. Rauterberg, Ernst W.; Lieberknecht, Hans-Michael; Wingen, Anne-Margret; Ritz, Eberhard // Kidney International;Mar1987, Vol. 31 Issue 3, p820 

    Antigens of the membrane attack complex of complement (MAC), such as C5, C6, C9 and MAC-related neoantigen(s), were demonstrated in the mesangium of 23 cases with IgA-glomerulonephritis (IgA-GN) and two cases with Henoch-Schönlein purpura nephritis (HSP). High specificity of the polyclonal...

  • Evidence-based classification of glomerular pathology. Cook, Terry; Roberts, Ian S D; Feehally, John; Barratt, Jonathan // Kidney International;Nov2014, Vol. 86 Issue 5, p1059 

    A letter to the editor is presented in response to an article about the Oxford Classification of IgA Nephropathy as evidence-based classification of glomerular disease.

  • Low incidence of IgA nephropathy in Blacks. Jennette, J. Charles; Wall, Sherri D.; Wilkman, Alice S. // Kidney International;Dec1985, Vol. 28 Issue 6, p944 

    The clinical and pathologic features were evaluated in 106 lgA nephropathy patients identified in 1.753 consecutive patients undergoing renal biopsy in the southeastern United States. Special attention was paid to the proportion of Blacks among the lgA nephropathy patients compared with non-IgA...

  • Evidence for IgA-specific B cell hyperactivity in patients with IgA nephropathy. Hale, Gerard M.; McIntosh, Sonia L.; Hiki, Yoshiyuki; Clarkson, Anthony R.; Woodroffe, Andrew J. // Kidney International;Mar1986, Vol. 29 Issue 3, p718 

    Spontaneous in vitro IgA synthesis by peripheral blood mononuclear cells (PBMC) of patients with IgA nephropathy was elevated; 419 ± 71 ng/106 cells (Mean ± SEM) compared with controls; 217 ± 35 (P < 0.02). Pokeweed mitogen (PWM) stimulated IgA synthesis was also elevated in patients:...

  • IgG subclasses in patients with membranoproliferative glomerulonephritis, membranous nephropathy, and lupus nephritis. Imai, Hirokazu; Hamai, Keiko; Komatsuda, Atsushi; Ohtani, Hiroshi; Miura, Akira B. // Kidney International;Jan1997, Vol. 51 Issue 1, p270 

    The article discusses the comparison of serum concentrations of IgG subclasses, the ratio of serum IgG subclass to total IgG, and glomerular deposition of IgG subclass between 7 membranoproliferative glomerulonephritis (MPGN) patients, 21 membranous nephropathy patients, and 9 lupus nephritis...

  • Nutcracker phenomenon in IgA nephropathy. Imai, Naohiko; Shirai, Sayuri; Shibagaki, Yugo; Kimura, Kenjiro // Clinical Kidney Journal;Jun2014, Vol. 7 Issue 3, p325 

    The article presents a case study of a 34-year-old Japanese woman with recurrent gross hematuria. Her medical history was unremarkable and was not taking any medications. Topics include hematuria and proteinuria, nutcracker phenomenon in IgA nephropathy and percutaneous kidney biopsy. It also...

  • Persistent microhaematuria with negative or low proteinuria. Gutiérrez, Eduardo; Moreno, Juan A.; Praga, Manuel // Nefrologia;2014, Vol. 34 Issue 1, p110 

    The level of proteinuria continues to be the clinical parameter that is best related to the development of long-term renal failure in glomerular pathologies. This quantity is particularly important when we analyse the progression of patients with IgA nephropathy. As such, the natural progression...

  • Strong association between IgA nephropathy and HLA-DR4 antigen. Kashiwabara, Hidehiko; Shishido, Hideo; Tomura, Shigeo; Tuchida, Hiroki; Miyajima, Tetsuya // Kidney International;Oct1982, Vol. 22 Issue 4, p377 

    Although the etiology and pathogenesis of IgA nephropathy is not fully understood, it has been classified as an immune-complex induced glomerulonephritis caused by an immunological mechanism. Forty-two patients with primary IgA nephropathy underwent tissue typing for HLA-A, B, and DR antigens by...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics