IgG Receptor Fc?RIIB Participates In Pathogenesis Of Kidney Injury Disease

Objective:To explore the effect of IgG Fc receptor IIB?Fc?RIIB?on the pathogenesis of kidney injury disease.Methods:Male mice of 8 weeks old were used for all experiments.The wide tpye?WT?and Fc?RIIB knock out(Fc?RIIB^-/-)mice on C57BL/6 background were randomly divided into two groups?Model and Control,n=5 per group?.Mice were intraperitoneally administrated with a single dose of 20 mg/Kg cisplatin for the acute kidney injury?AKI?mouse model induction and the control mice received identical volume of saline instead followed by the assessment of the AKI pathological performances focused on both the serum and renal tissues.Serum sample were proceeded to serum creatinine?Scr?and blood urea nitrogen?BUN?measurements.The kidney tissue injury were evaluated by HE-staining and immuno-histochemical analysis.Immuno-histochemical detection was performed on consecutive sections using the following antibodies?Abs?:CD68,pSTAT1 and c-Maf.Kidney homogenates were prepared for the evaluation of TNF-?,MCP-1,IL-6 and IL-10 using enzymelinked immunosorbent assay.Macrophage phenotyping and the expression of CCR5 were evaluated using flow cytometric analysis.Total RNA from kidneys was extracted for q-PCR analysis targeting CCL2,CCL3 and CCL4.Bone marrow cells were isolated from normal murine femurs,and cultured in DMEM supplemented with 10%FCS and 20 ng/ml GM-CSF for 6 days.Macrophages were determined by flow cytometric analysis for the expression of CD68 using an antibody targeting CD68.Macrophages were stimulated with 100 ng/ml LPS to M1 or 10 ng/ml IL-4 to M2,respectively.Macrophage phenotyping was evaluated using flow cytometric analysis.A total 84 subjects with end-stage renal diseases were recruited in this study,and blood samples from 84 subjects were collected for biochemical measurement as well as flow cytometric analysis for CCR5 expression and q-PCR analysis targeting Fc?RIIB.Renal function assessment 7 days after the renal transplantation was performed.Results:Cisplatin treatment induced higher levels of SCr and BUN in the serum and elevated inflammatory cytokines and chemokines?TNF-?,IL-6 and MCP-1?in the homogenate of renal tissue from Fc?RIIB^-/-mice compare to the WT mice.Semi-quantitative histological injury scores were significantly higher in cisplatin-treated Fc?RIIB deficient mice than their WT controls.Cisplatin injection induced increased macrophages and pSTAT1 infiltration in the mouse renal tissue,which was more apparent in mice lacking Fc?RIIB,whereas decreased c-Maf infiltration in the mouse renal tissue and similar frequencies of macrophage subtypes in the renal tissue from both mouse strains.Bone marrow-derived macrophage differentiated similarly in both mouse strains.The expression levels of human Fc?RIIB was negatively correlated to serum levels of the expression of CCR5in human with end-stage renal diseases.Conclusion:The current study suggested that IgG receptor Fc?RIIB deficiency enhanced cisplatin-induced Acute kidney injury.Enhanced Inflammatory cytokines expression and macrophages infiltration in mice lacking Fc?RIIB.The expression levels of human Fc?RIIB was negatively correlated to serum levels of the expression of CCR5 in human with end-stage renal diseases.