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Interaction of immune complexes with Fc receptors in mesangial cells: A potential target for the treatment of IgA nephropathy
Author(s) -
GÓMEZGUERRERO C.,
DUQUE N.,
LÓPEZARMADA MJ,
CASADO MT,
VIVANCO F.,
EGIDO J.
Publication year - 1997
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.1997.tb00197.x
Subject(s) - proinflammatory cytokine , mesangial cell , receptor , cytokine , immune system , monocyte , microbiology and biotechnology , nephritis , immune complex , immunology , biology , medicine , endocrinology , kidney , inflammation
Summary: Most human nephritis is caused by the deposition and/or formation of immune complexes in the glomerular region. Recently, it has been demonstrated that mesangial cells (MC) possess Fc receptors for IgG and IgA. In this work we demonstrate that catabolism of immune complexes occurs via Fc receptors. Mesangial cell incubation with IgA or IgG complexes induced cell proliferation and extracellular matrix synthesis, two key aspects of progressive renal diseases. These effects are in part due to the production of cytokines IL‐6 and transforming growth factor‐β (TGF‐β), as specific antibodies decreased thymidine incorporation and fibronectin (FN) production. Fc receptor stimulation induced several intracellular signals involving phospholipase Cγ activation, inositol trisphosphate (IP 3 ) formation, and Ca 2+ mobilization. Furthermore, we observed activation of the transcription factor NF‐κB, and increase in gene expression of monocyte chemoattractant protein‐1 (MCP‐1), proinflammatory cytokine participating in the recruitment of mononuclear cells, a phenomenon related to the onset and progression of renal injury. These responses depend on the Fc region of immunoglobulins because Fc fragments inhibited these effects. To observe whether this could be the case in vivo , rats with immune complex nephritis were treated with IgG Fc fragments. The administration of fragments significantly decreased proteinuria and morphological lesions. Our results show that MC activation through Fc receptors induces several intracellular responses, such as cell proliferation, synthesis of proinflammatory and profibrogenic cytokines, and accumulation of matrix proteins. • Modulation of immune complex—MC interaction by in vivo Fc fragments administration could represent a new approach in the glomerulonephritis treatment.