Differential expression of functional Fc-receptors and additional immune complex receptors on mouse kidney cells

Abstract

The precise mechanisms by which circulating immune complexes accumulate in the kidney to form deposits in glomerulonephritis are not well understood. In particular, the role of resident cells within glomeruli of the kidney has been widely debated. Immune complexes have been shown to bind one glomerular cell type (mesangial cells) leading to functional responses such as pro-inflammatory cytokine production. To further assess the presence of functional immunoreceptors on resident glomerular cells, cultured mouse renal epithelial, endothelial, and mesangial cells were treated with heat-aggregated mouse IgG or preformed murine immune complexes. Mesangial and renal endothelial cells were found to bind IgG complexes, whereas glomerular epithelial cell binding was minimal. A blocking antibody for Fc-gamma receptors reduced binding to mesangial cells but not renal endothelial cells, suggesting differential immunoreceptor utilization. RT-PCR and immunostaining based screening of cultured renal endothelial cells showed limited low-level expression of known Fc-receptors and Igbinding proteins. The interaction between mesangial cells and renal endothelial cells and immune complexes resulted in distinct, cell-specific patterns of chemokine and cytokine production. This novel pathway involving renal endothelial cells likely contributes to the predilection of circulating immune complex accumulation within the kidney and to the inflammatory responses that drive kidney injury.

Apoptotic Debris Accumulates on Hematopoietic Cells and Promotes Disease in Murine and Human Systemic Lupus Erythematosus

“…It is possible that passive transfer of anti-nucleosome IgG2a into AID −/− MRL/lpr mice induces deposits in the kidney independent of FcγRs by forming ICs with nuclear antigens that deposit on the glomerular basement membrane (53). However, since resident renal cells such as mesangial cells, podocytes, and renal endothelial cells do not express FcγRI (43), our data showed that lupus nephritis is dependent on constant binding of IgG-ICs to FcγRI expressed on hematopoietic cells. Whether disease depends on the secretion of FcγR-dependent cytokines, or signals that promote the migration of cells to the kidney is under investigation.…”

“…Together, the data show that after the early autoantibody response, chronic interaction of IgG-ICs and activating FcγRs amplifies the disease process. It also provides insight into how FcγRs on circulating myeloid cells, rather than kidney mesangial cells, might contribute to renal pathology in SLE (26, 43). …”

Neuraminidase activity mediates IL-6 production by activated lupus-prone mesangial cells

“…NEU1 and NEU3 are both endogenously expressed in MES13 cells, as detected by immunofluorescence (data not shown). MES13 MCs were treated with heat-aggregated IgG (HA-IgG), a mimic of immune complex deposition, shown to stimulate MCs to produce cytokines (14,45). However, increasing concentrations of HA-IgG failed to stimulate significant production of IL-6 or MCP-1 in MES13 MCs (Fig.…”

“…Here, our studies focused on IL-6 production following activation of lupus-prone MRL/lpr MCs using heat-aggregated IgG (HA-IgG) shown to bind and activate MCs, mimicking immune complex deposition (14,37,38,45), an early event in LN. In this report, we demonstrated that Neu1 expression, NEU activity, and IL-6 and MCP-1 production are significantly increased in lupus-prone MCs following activation.…”

Fcγ Receptors in Solid Organ Transplantation

“…Furthermore, FcγRIIB has been implicated in the pathogenesis of obesity-induced hypertension, via IgG-mediated attenuation of endothelial NO synthase activity [64]. The extent of FcγR expression on renal endothelial cells is less clear [65]. However, TNF-α and IFN-γ enhance FcγR expression by human endothelial cells in vitro, and this may have added importance in the context of allograft rejection [37].…”