Abnormal Immune Complex Processing and Spontaneous Glomerulonephritis in Complement Factor H-Deficient Mice with Human Complement Receptor 1 on Erythrocytes

Alexander, Jessy J.; Hack, Bradley K.; Chang, Anthony; Haas, Mark; Finberg, Robert W.; Quigg, Richard J.

doi:10.4049/jimmunol.1000683

Cited by 11 publications

(9 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this disease model, glomerular ICs contain apoferritin, IgG, and C3 components. 21 As in our past studies, 9 excessive glomerular IC deposition occurred when mice lacked platelet CfH, supporting that these formed from deposited ICs. Anti-apoferritin IgG and IgG-containing ICs were highest in CD11b −/− BM chimeric mice; although this did not translate into a higher quantity of total glomerular ICs, qualitatively there was greater extension into the peripheral capillary wall.…”

Section: Discussionsupporting

confidence: 79%

CD11b is protective in complement-mediated immune complex glomerulonephritis

Alexander

Chaves

Chang

et al. 2015

Kidney International

Self Cite

View full text Add to dashboard Cite

In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless plasma factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. Here we induced immune complex-mediated glomerulonephritis in CfH-/- mice chimeric for either wild type, CfH-/-, CD11b-/- and FcRγ-/- bone marrow stem cells. Glomerulonephritis was worse in CD11b-/- chimeras vs. all others, while disease in FcRγ-/- and wild type chimeras was comparable. Disease tracked strongly with humoral immune responses, but not glomerular immune complex deposits. Interstitial inflammation with M1 macrophages strongly correlated with glomerulonephritis scores. CD11b-/- chimeras had significantly more M1 macrophages and CD4+ T cells. The renal dendritic cell populations originating from bone marrow-derived CD11c+ cells were similar in all experimental groups. CD11b+ cells bearing colony stimulating factor 1 receptor were present in kidneys, including CD11b-/- chimeras; these cells correlated negatively with glomerulonephritis scores. Thus, experimental immune complex-mediated glomerulonephritis is associated with accumulation of M1 macrophages and CD4+ T cells in kidneys and functional renal insufficiency. Hence, CD11b on mononuclear cells is instrumental in generating an anti-inflammatory response in the inflamed kidney.

show abstract

Section: Discussionsupporting

confidence: 79%

CD11b is protective in complement-mediated immune complex glomerulonephritis

Alexander

Chaves

Chang

et al. 2015

Kidney International

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cfh − / − mice were divided into three groups of six mice each. Group 1: mice were treated with saline and served as controls; Group 2: immune complex glomerulonephritis was induced by immunizing 6‐ to 8‐week‐old male Cfh −/− mice ( n = 6) for 5 weeks with a daily intraperitoneal dose of 4 mg horse spleen apoferritin, as described previously . Group 3: mice were treated intraperitoneally with apoferritin and CMN obtained from Calbiochem, 30 mg/kg.…”

Section: Methodsmentioning

confidence: 99%

Curcumin alleviates immune‐complex‐mediated glomerulonephritis in factor‐H‐deficient mice

et al. 2013

Self Cite

View full text Add to dashboard Cite

SummaryComplement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective antiinflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh À/À ) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45Á4 AE 7Á5 versus 35Á6 AE 5Á1; albuminuria, 50Á1 AE 7Á1 versus 15Á7 AE 7Á1; glomerulonephritis, 2Á62 + 0Á25 versus 2 + 0Á3, P < 0Á05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19 + B cells and the ratio of CD19 : CD3 cells (P < 0Á05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-b and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness.

show abstract

“…The first mechanism is deposition of preformed serum ICs [12]. This mechanism is hard to confirm, as ICs are difficult to isolate or quantify in lupus patient sera and thus are not felt to play a major role in the pathogenesis of lupus nephritis.…”

Section: Autoantibodies and Renal Immune Complex Depositionmentioning

confidence: 99%

Mechanisms of tissue injury in lupus nephritis

2011

View full text Add to dashboard Cite

Systemic lupus erythematosus is a prototypic autoimmune disease characterized by autoantibody production and immune complex formation/deposition in target organs such as the kidney. Resultant local inflammation then leads to organ damage. Nephritis, a major cause of morbidity and mortality in patients with lupus, occurs in approximately 50% of lupus patients. In the present review, we provide an overview of the current research and knowledge concerning mechanisms of renal injury in both lupus-prone mouse models and human lupus patients.

show abstract

Abnormal Immune Complex Processing and Spontaneous Glomerulonephritis in Complement Factor H-Deficient Mice with Human Complement Receptor 1 on Erythrocytes

Abstract: Material

Cited by 11 publications

References 35 publications

CD11b is protective in complement-mediated immune complex glomerulonephritis

CD11b is protective in complement-mediated immune complex glomerulonephritis

Curcumin alleviates immune‐complex‐mediated glomerulonephritis in factor‐H‐deficient mice

Mechanisms of tissue injury in lupus nephritis

Contact Info

Product

Resources

About