Expression of the protein Annexin A2 in the kidney after ischaemia/reperfusion enhances binding of factor H and inhibition of the alternative complement pathway

Coleman, Kathrin E.; Renner, Brandon; Ferreira, Viviana P.; Cortés, Claudio; Pangburn, Michael K.; Tomlinson, Stephen; Holers, Michael; Thurman, Joshua M.

doi:10.1016/j.molimm.2008.08.049

Cited by 3 publications

(4 citation statements)

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“…The relevance of the role of annexin-II in pathology is unclear, but autoantibodies against annexin-II have been found in patients with systemic lupus erythematosus and other autoimmune diseases (44). Annexin-II has recently been identified as an fH binding partner in a mouse ischemia/reperfusion model (17). The authors hypothesized that annexin-II directs fH to ischemic renal cells and mediates their protection.…”

Section: Discussionmentioning

confidence: 99%

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Annexin-II, DNA, and Histones Serve as Factor H Ligands on the Surface of Apoptotic Cells

Leffler

Herbert

Norström

et al. 2010

Journal of Biological Chemistry

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Apoptotic cells are opsonized by complement components such as C1q and C3b, which increases their susceptibility to phagocytosis. Soluble complement inhibitors such as factor H (fH) also recognize apoptotic cells to minimize the pro-inflammatory effects of downstream complement activation. We used four radiolabeled protein constructs that span different regions of the 20 complement control protein (CCP) modules that make up fH and found that fragments comprising CCPs 6–8, CCPs 8–15, and CCPs 19–20 but not CCPs 1–4, bound to apoptotic Jurkat T cells. There are four possible ligand types on apoptotic cells that could recruit fH: proteins, carbohydrates, lipids, and DNA. We found that CCPs 6–8 of fH bind to annexin-II, a trypsin-insensitive protein that becomes exposed on surfaces of apoptotic cells. The second ligand of fH, which interacts with CCPs 6–8 and 19–20, is DNA. Confocal microscopy showed co-localization of fH with antibodies specific for DNA. fH also binds to histones devoid of DNA, and CCPs 1–4, 6–8, and 8–15 mediate this interaction. Treatment of apoptotic cells with neuraminidase, chondroitinase, heparitinase, and heparinase did not change fH binding. Treatment of apoptotic cells with phospholipase A2 dramatically increased both binding of fH and cell-surface DNA. We also excluded the possibility that fH interacts with lysophospholipids using surface plasmon resonance and flow cytometry with lipid-coated beads. Identification of annexin-II as one of the fH ligands on apoptotic cells together with the fact that autoantibodies against annexin-II are found in systemic lupus erythematosus provides further insight into understanding the pathogenesis of this disease.

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Section: Discussionmentioning

confidence: 99%

“…We found at least three ligands for fH on apoptotic cells: DNA, histones, and the phospholipid-binding protein annexin-II, which has recently been suggested as a fH-binding partner in a mouse ischemia/reperfusion model (17). …”

Section: Introductionmentioning

confidence: 86%

Annexin-II, DNA, and Histones Serve as Factor H Ligands on the Surface of Apoptotic Cells

Leffler

Herbert

Norström

et al. 2010

Journal of Biological Chemistry

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“…DNA was first identified as having two major binding proteins, factor H and factor B over 30 years ago, when human serum was fractionated by affinity chromatography on DNA-cellulose (Gardner et al, 1980). Annexin II, an abundant phospholipid binding protein that is present in the cytosol and on the cytoplasmic face of plasma membrane and early endosomes (Moss, 1992), was initially suggested as a possible ligand for factor H that is expressed in the post-ischemic kidney (Coleman et al, 2010). In addition, soluble acute phase proteins, C-reactive protein (Mold et al, 1999; Okemefuna et al, 2010) and pentraxin 3 (Deban et al, 2008) have been reported to have the ability to bind to apoptotic cells and recruit factor H to that cell surface (Deban et al, 2008; Gershov et al, 2000).…”

Section: Factor H As An Alternative Pathway Host Recognition Molecmentioning

confidence: 99%

Complement control protein factor H: The good, the bad, and the inadequate

Ferreira

Pangburn

Cortés

2010

Molecular Immunology

370

357

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The complement system is an essential component of the innate immune system that participates in elimination of pathogens and altered host cells and comprises an essential link between the innate and adaptive immune system. Soluble and membrane-bound complement regulators protect cells and tissues from unintended complement-mediated injury. Complement factor H is a soluble complement regulator essential for controlling the alternative pathway in blood and on cell surfaces. Normal recognition of self cell markers (i.e. polyanions) and C3b/C3d fragments is necessary for factor H function. Inadequate recognition of host cell surfaces by factor H due to mutations and polymorphisms have been associated with complement-mediated tissue damage and disease. On the other hand, unwanted recognition of pathogens and altered self cells (i.e. cancer) by factor H is used as an immune evasion strategy. This review will focus on the current knowledge related to these versatile recognition properties of factor H.

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“…It has been demonstrated that Crry, normally found on the basolateral side of tubular cells along the basement membrane, was sequestered in the tubular lumen upon ischaemic insult, allowing increased complement deposition and injury on these cells 48 . Additionally, changes in the cell membrane structural integrity and exposure of neoepitopes may alter the binding kinetics of the fluid‐phase complement regulator fH, which can also impact on complement activation and renal IRI 49,50 …”

Section: Complement and Kidney Diseasesmentioning

confidence: 99%

Review: Complement and its regulatory proteins in kidney diseases

Lesher

Song

2010

Nephrology

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Complement is a part of the body’s innate immune system that helps defend the host from microbial infection. It is tightly controlled by a number of cell surface and fluid-phase proteins so that under normal circumstances injury to autologous tissues is avoided. In many pathological settings, such as when the complement regulatory mechanisms are dysfunctional or overwhelmed, complement attack of autologous tissues can occur with severe, sometimes life-threatening consequences. The kidney appears to be particularly vulnerable to complement-mediated inflammatory injury and many kidney pathologies have been linked to abnormal complement activation. Clinical and experimental studies have shown that complement attack can be a primary cause in rare, genetically predisposed kidney diseases or a significant contributor to kidney injury caused by other etiological factors. Here we provide a brief review of recent advances on the activation and regulation of the complement system in kidney disease, with a particular emphasis on the relevance of complement regulatory proteins.

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Expression of the protein Annexin A2 in the kidney after ischaemia/reperfusion enhances binding of factor H and inhibition of the alternative complement pathway

Cited by 3 publications

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Annexin-II, DNA, and Histones Serve as Factor H Ligands on the Surface of Apoptotic Cells

Annexin-II, DNA, and Histones Serve as Factor H Ligands on the Surface of Apoptotic Cells

Complement control protein factor H: The good, the bad, and the inadequate

Review: Complement and its regulatory proteins in kidney diseases

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