Soluble IgA and IgG aggregates are catabolized by cultured rat mesangial cells and induce production of TNF-alpha and IL-6, and proliferation.
IgA nephropathy, a primary glomerulonephritis, is principally characterized by mesangial deposits of IgA immune complexes. Recently, it has been demonstrated that cultured glomerular mesangial cells (MC) express Fc alpha and Fc gamma receptors. In this work, we studied whether the interaction of soluble aggregates of IgA and IgG (AIgA and AIgG) with MC triggers a number of responses, including generation and release of inflammatory mediators, cell proliferation, and catabolism of the complexes. Aggregates bound to MC and were catabolized in a time-dependent manner. The percentage of cell-associated or -degraded proteins decreased in the presence of Fc, but not with Fab fragments. Both AIgA and AIgG elicited the synthesis and release of TNF-alpha and IL-6 in a dose-dependent manner, reaching a maximum between 6 and 12 h, respectively. Northern blot analysis showed that both aggregates induced the expression of mRNA encoding TNF-alpha and IL-6. Because MC proliferation is a morphologic feature commonly observed in patients with IgA nephropathy, we examined whether immune aggregates could be involved in this phenomenon. Both AIgA and AIgG induced an increase in MC number, assessed by [3H]thymidine and methylene blue uptake. The presence of anti-TNF-alpha or anti-IL-6 Abs in the medium decreased the proliferative effect triggered by aggregates. These results show that Fc alpha and Fc gamma receptor occupancy of MC induces the synthesis and release of inflammatory cytokines and proliferation, as well as the phagocytosis of stimulatory proteins. These findings could have implications for the understanding of inflammation and repair in IgA nephropathy.
Renal Division, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
C
C
Gómez-Guerrero
M J
MJ
López-Armada
E
E
González
J
J
Egido
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000276:immunology*; D005922:Glomerulonephritis, IGA / Q000276:immunology; D007070:Immunoglobulin A / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha