Calreticulin, a Potential Cell Surface Receptor Involved in Cell Penetration of Anti-DNA Antibodies

Seddiki, Nabila; Nato, Farida; Lafaye, Pierre; Amoura, Zahir; Piette, Jean Charles; Mazié, J. C.

doi:10.4049/jimmunol.166.10.6423

Cited by 49 publications

(42 citation statements)

References 50 publications

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“…The experiments were conducted under serum-free (AIM-V) conditions to exclude any interference by exogenous proteins and peptides. CRT has previously been shown to be expressed on activated T cells (27) and also detected in 75-100% of the T cells in our experiments.…”

Section: The Tsp-1 Binding Site In Crt Triggers T Cell Migration Intosupporting

confidence: 75%

Autocrine Regulation of T Cell Motility by Calreticulin-Thrombospondin-1 Interaction

Forslöw

Sundqvist

2005

The Journal of Immunology

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The mechanisms regulating T lymphocyte migration within the extracellular matrix are not understood. We show in this study that the thrombospondin-1 binding site of calreticulin, spanning aa 19–32, is a major triggering factor for T cell motility and migration within a three-dimensional collagen type 1 matrix, and that exogenous motogenic factors such as chemokines can stimulate migration via a calreticulin-thrombospondin-1 pathway. Endogenous calreticulin binding to the N-terminal domain of endogenous thrombospondin-1 elicited a motogenic signal to the T cells through the C-terminal domain of thrombospondin-1 and its cell surface receptor integrin-associated protein (CD47). Our data further revealed that thrombospondin-1 was expressed on the cell surface with a high turnover, and that PI3K and the Janus family of tyrosine kinases were required for T cell motility mediated through calreticulin, thrombospondin-1, and CD47. These results unveil an autocrine mechanism of calreticulin-thrombospondin-1-CD47 interaction for the control of T cell motility and migration within three-dimensional extracellular matrix substrata.

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Section: The Tsp-1 Binding Site In Crt Triggers T Cell Migration Intosupporting

confidence: 75%

Autocrine Regulation of T Cell Motility by Calreticulin-Thrombospondin-1 Interaction

Forslöw

Sundqvist

2005

The Journal of Immunology

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“…The calreticulin (CALR) protein binds to misfolded proteins and has been previously reported to be associated with systemic lupus and other autoimmune disorders through its binding to autoantibodies (46,47) and DNA (48). The F-box and leucine-rich repeat protein FBXL19 is associated with cellular inflammation (pulmonary) through its action as a ubiquitin ligase to target proteins for proteasomal degradation (49).…”

Section: Discussionmentioning

confidence: 99%

The Identification of Novel Potential Injury Mechanisms and Candidate Biomarkers in Renal Allograft Rejection by Quantitative Proteomics

Sigdel

Salomonis

Nicora

et al. 2014

Molecular & Cellular Proteomics

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Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n ‫؍‬ 74), stable graft (STA) (n ‫؍‬ 74), chronic allograft injury (CAI) (n ‫؍‬ 58), BK virus nephritis (BKVN) (n ‫؍‬ 38), nephrotic syndrome (NS) (n ‫؍‬ 8), and healthy, normal control (HC) (n ‫؍‬ 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p < 0.05) with a significant finding that SUMO2 (small ubiquitin-related modifier 2) was identified as a "hub" protein for graft injury irrespective of causation. Sixtynine urine proteins had differences in abundance (p < 0.01) in AR compared with stable graft, of which 12 proteins were up-regulated in AR with a mean fold increase of 2.8. Nine urine proteins were highly specific for AR because of their significant differences (p < 0.01; fold increase >1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p ‫؍‬ 0.04), fibrinogen gamma (FGG; p ‫؍‬ 0.03), and HLA DRB1 (p ‫؍‬ 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p ‫؍‬ 0.03, FGG p ‫؍‬ 0.02), a finding that supports the utility of monitoring these urinary proteins for the specific and sensitive noninvasive diagnosis of acute renal allograft rejection. Molecular & Cellular Proteomics

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“…Madaio and colleagues (18) described a 110-kDa protein identified as myosin 1 that was immunoprecipitated by a murine anti-DNA mAb from rat hepatoma cells. Seddiki (19) reported that a 50-kDa receptor on human lymphocyte cell lines identified as calreticulin may mediate the cellular penetration of some anti-DNA Abs. Most recently, Eilat and coworkers (6) demonstrated that five pathogenic anti-dsDNA Abs isolated from (NZB ϫ NZW)F 1 mice cross-reacted with ␣-actinin, while two mAbs which were nonpathogenic did not.…”

Section: Discussionmentioning

confidence: 99%

α-Actinin Is a Cross-Reactive Renal Target for Pathogenic Anti-DNA Antibodies

Deocharan¹,

Qing

Lichauco

et al. 2002

The Journal of Immunology

190

167

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Anti-DNA Abs commonly found in patients with systemic lupus erythematosus are thought to play an important pathogenic role in lupus nephritis. Anti-DNA Abs may contribute to renal disease by cross-reactivity with renal Ags, the identity of which remain elusive. To identify a target Ag for pathogenic anti-DNA Abs, we performed Western blotting and immunoprecipitations of mesangial cell lysates from the lupus-prone MRL-lpr/lpr mouse and a nonautoimmune BALB/c mouse with the pathogenic anti-DNA Ab R4A. We found that R4A (but not a nonpathogenic Ab mutant of R4A) binds to and immunoprecipitates a 100-kDa protein expressed on the cell surface and in lysates of MRL-lpr/lpr mesangial cells. DNase treatment of the lysate and of the R4A Ab did not effect binding, indicating that the binding of R4A to the 100-kDa protein was direct and not mediated by an antigenic bridge containing DNA. Binding was greatly diminished in BALB/c lysates, suggesting that Ag expression or availability at the level of the target organ may be a factor in determining susceptibility to lupus nephritis. Following identification of this 100-kDa protein as nonmuscle α-actinin, binding of R4A to α-actinin was confirmed by Western blot, ELISA, inhibition studies, and immunofluorescence. High titers of anti-α-actinin Abs were present in sera and kidney eluates of lupus mice with active nephritis. These results indicate that the nephritogenicity of some anti-DNA Abs may be mediated via cross-reactivity with α-actinin. Furthermore, variations in target Ag display between individuals may underlie differential susceptibility to anti-DNA Ab-induced renal disease.

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Calreticulin, a Potential Cell Surface Receptor Involved in Cell Penetration of Anti-DNA Antibodies

Cited by 49 publications

References 50 publications

Autocrine Regulation of T Cell Motility by Calreticulin-Thrombospondin-1 Interaction

Autocrine Regulation of T Cell Motility by Calreticulin-Thrombospondin-1 Interaction

The Identification of Novel Potential Injury Mechanisms and Candidate Biomarkers in Renal Allograft Rejection by Quantitative Proteomics

α-Actinin Is a Cross-Reactive Renal Target for Pathogenic Anti-DNA Antibodies

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