Endothelial cell activation by antiphospholipid antibodies is modulated by Kruppel-like transcription factors.

Abstract:

:Antiphospholipid syndrome is characterized by thrombosis and/or recurrent pregnancy loss in the presence of antiphospholipid antibodies (APLAs). The majority of APLAs are directed against phospholipid-binding proteins, particularly β₂-glycoprotein I (β₂GPI). Anti-β₂GPI antibodies activate endothelial cells in a β₂GPI-dependent manner through a pathway that involves NF-κB. Krüppel-like factors (KLFs) play a critical role in regulating the endothelial response to inflammatory stimuli. We hypothesized that activation of endothelial cells by APLA/anti-β₂GPI antibodies might be associated with decreased expression of KLFs, which in turn might facilitate cellular activation mediated through NF-κB. Our experimental results confirmed this hypothesis, demonstrating markedly decreased expression of KLF2 and KLF4 after incubation of cells with APLA/anti-β₂GPI antibodies. Restoration of KLF2 or KLF4 levels inhibited NF-κB transcriptional activity and blocked APLA/anti-β₂GPI-mediated endothelial activation despite NF-κB p65 phosphorylation. Chromatin immunoprecipitation analysis demonstrated that inhibition of NF-κB transcriptional activity by KLFs reflects sequestration of the cotranscriptional activator CBP/p300, making this cofactor unavailable to NF-κB. These findings suggest that the endothelial response to APLA/anti-β₂GPI antibodies reflects competition between KLFs and NF-κB for their common cofactor, CBP/p300. Taken together, these observations are the first to implicate the KLFs as novel participants in the endothelial proinflammatory response to APLA/anti-β₂GPI antibodies.

journal_name

Blood

journal_title

Blood

authors

Allen KL,Hamik A,Jain MK,McCrae KR

doi

10.1182/blood-2010-10-313072

subject

Has Abstract

pub_date

2011-06-09 00:00:00

pages

6383-91

issue

23

eissn

0006-4971

issn

1528-0020

pii

blood-2010-10-313072

journal_volume

117

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Analysis of leukocyte differentiation antigens in blood and bone marrow from preleukemia (refractory anemia) patients using monoclonal antibodies.

    abstract::Peripheral blood and bone marrow mononuclear cells from patients with refractory anemia (RA) or RA with sideroblasts (defined according to the revised French-American-British classification with less than 5% blast cells in the bone marrow) were analyzed using a panel of monoclonal antibodies directed against leukocyte...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hokland P,Kerndrup G,Griffin JD,Ellegaard J

    更新日期:1986-04-01 00:00:00

  • Defective targeting of hemojuvelin to plasma membrane is a common pathogenetic mechanism in juvenile hemochromatosis.

    abstract::Hemojuvelin (HJV) positively modulates the iron regulator hepcidin, and its mutations are the major cause of juvenile hemochromatosis (JH), a recessive disease leading to iron overload. Defective HJV reduces hepcidin up-regulation both in humans and in Hjv-deficient mice. To investigate the JH pathogenesis and the fun...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-08-041004

    authors: Silvestri L,Pagani A,Fazi C,Gerardi G,Levi S,Arosio P,Camaschella C

    更新日期:2007-05-15 00:00:00

  • Culture of human fetal B-cell precursors on bone marrow stroma maintains highly proliferative CD20dim cells.

    abstract::Growth of human B-cell precursors (BCP) was achieved by plating fetal CD10+ surface-mu (s mu)- cells in liquid medium onto bone marrow-derived fibroblastic stromal cell layers deprived of hematopoietic cells. Proliferation of the fetal BCP was strongly potentiated by the addition of interleukin-7 (IL-7) to the culture...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Moreau I,Duvert V,Banchereau J,Saeland S

    更新日期:1993-03-01 00:00:00

  • Gene cloning of rat and mouse platelet glycoprotein V: identification of megakaryocyte-specific promoters and demonstration of functional thrombin cleavage.

    abstract::Platelet glycoprotein (GP) V is a major surface protein cleaved during thrombin-induced platelet activation. GPV associates noncovalently with the GPIb-IX complex to form GPIb-V-IX, a receptor for von Willebrand factor and thrombin. We describe the cloning of the genes coding for rat and mouse GPV and compare them wit...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ravanat C,Morales M,Azorsa DO,Moog S,Schuhler S,Grunert P,Loew D,Van Dorsselaer A,Cazenave JP,Lanza F

    更新日期:1997-05-01 00:00:00

  • Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes.

    abstract::The mutation status and usage of specific VH genes such as V3-21 and V1-69 are potentially independent pathogenic and prognostic factors in chronic lymphocytic leukemia (CLL). To investigate the role of antigenic stimulation, we analyzed the expression of genes involved in B-cell receptor (BCR) signaling/activation, c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-04-1483

    authors: Kienle D,Benner A,Kröber A,Winkler D,Mertens D,Bühler A,Seiler T,Jäger U,Lichter P,Döhner H,Stilgenbauer S

    更新日期:2006-03-01 00:00:00

  • 2-Chlorodeoxyadenosine: an effective new agent for the treatment of chronic lymphocytic leukemia.

    abstract::2-Chlorodeoxyadenosine, a new lymphocyte-selective, anti-neoplastic drug was administered to 18 patients with advanced chronic lymphocytic leukemia of B-cell origin. All patients were resistant to conventional treatment. A total of 44 courses of 2-chlorodeoxyadenosine were completed with minimal toxicity. An overall r...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Piro LD,Carrera CJ,Beutler E,Carson DA

    更新日期:1988-09-01 00:00:00

  • Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma.

    abstract::Little is known about mechanisms involved in skin-specific homing of cutaneous T-cell lymphoma (CTCL). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites. We investigated tissue samples and tumor cell suspensions of patients with CD30(+) CTCL (n = 8) ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-02-0475

    authors: Kleinhans M,Tun-Kyi A,Gilliet M,Kadin ME,Dummer R,Burg G,Nestle FO

    更新日期:2003-02-15 00:00:00

  • Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion.

    abstract::Secretion of platelet granules is necessary for normal hemostasis. Platelet secretion requires soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) complex formation between different members of the syntaxin, SNAP-25, and vesicle-associated membrane protein (VAMP) gene families. Using m...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v100.3.1081

    authors: Polgár J,Chung SH,Reed GL

    更新日期:2002-08-01 00:00:00

  • EPO-mediated expansion of late-stage erythroid progenitors in the bone marrow initiates recovery from sublethal radiation stress.

    abstract::Erythropoiesis is a robust process of cellular expansion and maturation occurring in murine bone marrow and spleen. We previously determined that sublethal irradiation, unlike bleeding or hemolysis, depletes almost all marrow and splenic erythroblasts but leaves peripheral erythrocytes intact. To better understand the...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-11-394304

    authors: Peslak SA,Wenger J,Bemis JC,Kingsley PD,Koniski AD,McGrath KE,Palis J

    更新日期:2012-09-20 00:00:00

  • Aurora-A kinase: a novel target of cellular immunotherapy for leukemia.

    abstract::Aurora-A kinase (Aur-A) is a member of the serine/threonine kinase family that regulates the cell division process, and has recently been implicated in tumorigenesis. In this study, we identified an antigenic 9-amino-acid epitope (Aur-A(207-215): YLILEYAPL) derived from Aur-A capable of generating leukemia-reactive cy...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-06-164889

    authors: Ochi T,Fujiwara H,Suemori K,Azuma T,Yakushijin Y,Hato T,Kuzushima K,Yasukawa M

    更新日期:2009-01-01 00:00:00

  • Enhancement of the biologic effects of interleukin-3 in vivo by anti-interleukin-3 antibodies.

    abstract::Interleukin-3 (IL-3) has been shown to be a promising agent in the stimulation of bone marrow regeneration following myeloablative therapy. The biologic half-life of this agent is very short (5 to 15 minutes), which limits the effectiveness of low-dose therapy. Here we show that the biologic effects of low-dose IL-3 i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Jones AT,Ziltener HJ

    更新日期:1993-08-15 00:00:00

  • IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors.

    abstract::Long-living memory stem T cells (T(SCM)) with the ability to self-renew and the plasticity to differentiate into potent effectors could be valuable weapons in adoptive T-cell therapy against cancer. Nonetheless, procedures to specifically target this T-cell population remain elusive. Here, we show that it is possible ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-05-431718

    authors: Cieri N,Camisa B,Cocchiarella F,Forcato M,Oliveira G,Provasi E,Bondanza A,Bordignon C,Peccatori J,Ciceri F,Lupo-Stanghellini MT,Mavilio F,Mondino A,Bicciato S,Recchia A,Bonini C

    更新日期:2013-01-24 00:00:00

  • Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation.

    abstract::This study demonstrates that the human platelet F11 receptor (F11R) functions as an adhesion molecule, and this finding is confirmed by the structure of the protein as revealed by molecular cloning. The F11R is a 32-/35-kd protein duplex that serves as the binding site through which a stimulatory monoclonal antibody c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sobocka MB,Sobocki T,Banerjee P,Weiss C,Rushbrook JI,Norin AJ,Hartwig J,Salifu MO,Markell MS,Babinska A,Ehrlich YH,Kornecki E

    更新日期:2000-04-15 00:00:00

  • Elimination of acute myelogenous leukemic cells from marrow and tumor suspensions in the rat with 4-hydroperoxycyclophosphamide.

    abstract::Cell suspensions of normal rat marrow mixed with rat acute myelogenous leukemic cells were prepared and incubated in vitro with graded doses of 4-hydroperoxycyclophosphamide (4HC). The cell suspensions were injected into rats prepared with a lethal dose of total body irradiation. Animals injected with these cells surv...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sharkis SJ,Santos GW,Colvin M

    更新日期:1980-03-01 00:00:00

  • Growth and development following marrow transplantation for leukemia.

    abstract::One hundred forty-two patients between the ages of 1 and 17 years who survived disease-free more than 1 year after marrow transplantation for hematologic malignancy had growth and development evaluations from one to 14 years posttransplant (median 4 years). Prior to transplant all children received multiagent chemothe...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sanders JE,Pritchard S,Mahoney P,Amos D,Buckner CD,Witherspoon RP,Deeg HJ,Doney KC,Sullivan KM,Appelbaum FR

    更新日期:1986-11-01 00:00:00

  • AID-associated DNA repair pathways regulate malignant transformation in a murine model of BCL6-driven diffuse large B-cell lymphoma.

    abstract::Somatic hypermutation and class-switch recombination of the immunoglobulin (Ig) genes occur in germinal center (GC) B cells and are initiated through deamination of cytidine to uracil by activation-induced cytidine deaminase (AID). Resulting uracil-guanine mismatches are processed by uracil DNA glycosylase (UNG)-media...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-02-628164

    authors: Gu X,Booth CJ,Liu Z,Strout MP

    更新日期:2016-01-07 00:00:00

  • Activation-dependent alpha5beta1 integrin-mediated adhesion to fibronectin decreases proliferation of chronic myelogenous leukemia progenitors and K562 cells.

    abstract::Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell characterized by abnormal circulation and proliferation of malignant progenitors. In contrast to their normal counterparts, CML progenitors adhere poorly to bone marrow stroma or fibronectin (FN). Aside from anchoring progenitors ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lundell BI,McCarthy JB,Kovach NL,Verfaillie CM

    更新日期:1996-03-15 00:00:00

  • Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo.

    abstract::Dickkopf-1 (DKK1), a soluble inhibitor of Wnt signaling secreted by multiple myeloma (MM) cells contributes to osteolytic bone disease by inhibiting the differentiation of osteoblasts. In this study, we tested the effect of anti-DKK1 therapy on bone metabolism and tumor growth in a SCID-rab system. SCID-rab mice were ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-09-047712

    authors: Yaccoby S,Ling W,Zhan F,Walker R,Barlogie B,Shaughnessy JD Jr

    更新日期:2007-03-01 00:00:00

  • Mechanisms of action of ruxolitinib in murine models of hemophagocytic lymphohistiocytosis.

    abstract::Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal disorder characterized by the overactivation of T cells and macrophages that excessively produce proinflammatory cytokines, including interferon-γ (IFN-γ). Previously, we reported that the JAK inhibitor ruxolitinib dampens T-cell activation and lessens inflamm...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2019000761

    authors: Albeituni S,Verbist KC,Tedrick PE,Tillman H,Picarsic J,Bassett R,Nichols KE

    更新日期:2019-07-11 00:00:00

  • Trafficking of the major virulence factor to the surface of transfected P. falciparum-infected erythrocytes.

    abstract::After invading human red blood cells (RBCs) the malaria parasite Plasmodium falciparum remodels the host cell by trafficking proteins to the RBC compartment. The virulence protein P. falciparum erythrocyte membrane protein 1 (PfEMP1) is responsible for cytoadherence of infected cells to host endothelial receptors. Thi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-12-4666

    authors: Knuepfer E,Rug M,Klonis N,Tilley L,Cowman AF

    更新日期:2005-05-15 00:00:00

  • Structural, functional, and tissue distribution analysis of human transferrin receptor-2 by murine monoclonal antibodies and a polyclonal antiserum.

    abstract::Human transferrin receptor-2 (TFR-2) is a protein highly homologous to TFR-1/CD71 and is endowed with the ability to bind transferrin (TF) with low affinity. High levels of TFR-2 mRNA were found in the liver and in erythroid precursors. Mutations affecting the TFR-2 gene led to hemochromatosis type 3, a form of inheri...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-01-0076

    authors: Deaglio S,Capobianco A,Calì A,Bellora F,Alberti F,Righi L,Sapino A,Camaschella C,Malavasi F

    更新日期:2002-11-15 00:00:00

  • Neddylation plays an important role in the regulation of murine and human dendritic cell function.

    abstract::Posttranslational protein modifications (PTMs) are necessary for cells to function properly. The role of PTMs in regulating immune responses, specifically those mediated by dendritic cells (DCs), which are critical for both innate and adaptive immunity, is not well understood. Utilizing multiple but complementary appr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-02-486373

    authors: Mathewson N,Toubai T,Kapeles S,Sun Y,Oravecz-Wilson K,Tamaki H,Wang Y,Hou G,Sun Y,Reddy P

    更新日期:2013-09-19 00:00:00

  • Caspase activation is required for nitric oxide-mediated, CD95(APO-1/Fas)-dependent and independent apoptosis in human neoplastic lymphoid cells.

    abstract::Nitric oxide (NO), an important effector molecule involved in immune regulation and host defense, was shown to induce apoptosis in lymphoma cells. In the present report the NO donor glycerol trinitrate was found to induce apoptosis in Jurkat cells that are sensitive to CD95-mediated kill. In contrast, a CD95-resistant...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chlichlia K,Peter ME,Rocha M,Scaffidi C,Bucur M,Krammer PH,Schirrmacher V,Umansky V

    更新日期:1998-06-01 00:00:00

  • Long-term suspension cultures of human cord blood myeloid cells.

    abstract::A method is described that allows for the routine long-term (greater than 3 mo) growth of normal, immature human myeloid cells in liquid suspension culture. The techniques employ cell separation, utilization of special growth conditions (RPMI with hydrocortisone and vitamin D), and cord blood as the source of leukocyt...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Salahuddin SZ,Markham PD,Ruscetti FW,Gallo RC

    更新日期:1981-11-01 00:00:00

  • Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo.

    abstract::Endothelial progenitor cells are critically involved in essential biologic processes, such as vascular homeostasis, regeneration, and tumor angiogenesis. Endothelial colony-forming cells (ECFCs) are endothelial progenitor cells with robust proliferative potential. Their profound vessel-forming capacity makes them a pr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-09-181362

    authors: Reinisch A,Hofmann NA,Obenauf AC,Kashofer K,Rohde E,Schallmoser K,Flicker K,Lanzer G,Linkesch W,Speicher MR,Strunk D

    更新日期:2009-06-25 00:00:00

  • Molecular analysis of the structure and expression of the RH locus in individuals with D--, Dc-, and DCw- gene complexes.

    abstract::Rh blood group antigens of the D, C/c, and E/e series are carried by at least three red cell membrane polypeptides encoded by two highly related genes, RHD and RHCE. Homozygous individuals carrying the D--, Dc-, and DCw- gene complexes are characterized by a total or partial lack of expression of the RHCE-encoded anti...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chérif-Zahar B,Raynal V,D'Ambrosio AM,Cartron JP,Colin Y

    更新日期:1994-12-15 00:00:00

  • Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?

    abstract::Recent molecular analyses of leukemic blasts from pretreatment marrow or blood of patients with acute myeloid leukemia (AML) and a normal karyotype, the largest cytogenetic subset (ie, 40%-49%) of AML, have revealed a striking heterogeneity with regard to the presence of acquired gene mutations and changes in gene exp...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2006-06-001149

    authors: Mrózek K,Marcucci G,Paschka P,Whitman SP,Bloomfield CD

    更新日期:2007-01-15 00:00:00

  • Synthetic anti-BR3 antibodies that mimic BAFF binding and target both human and murine B cells.

    abstract::BR3, which is expressed on all mature B cells, is a specific receptor for the B-cell survival and maturation factor BAFF (B-cell-activating factor belonging to the tumor necrosis factor [TNF] family). In order to investigate the consequences of targeting BR3 in murine models and to assess the potential of BR3 antibodi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-03-011031

    authors: Lee CV,Hymowitz SG,Wallweber HJ,Gordon NC,Billeci KL,Tsai SP,Compaan DM,Yin J,Gong Q,Kelley RF,DeForge LE,Martin F,Starovasnik MA,Fuh G

    更新日期:2006-11-01 00:00:00

  • The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor.

    abstract::A plethora of myeloma growth factors (MGFs) has been identified, but their relative importance and cooperation have not been determined. We investigated 5 MGFs (interleukin-6 [IL-6], insulin-like growth factor type 1 [IGF-1], hepatocyte growth factor [HGF], HB-epidermal growth factor [HB-EGF], and a proliferation-indu...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-07-170464

    authors: Sprynski AC,Hose D,Caillot L,Réme T,Shaughnessy JD Jr,Barlogie B,Seckinger A,Moreaux J,Hundemer M,Jourdan M,Meissner T,Jauch A,Mahtouk K,Kassambara A,Bertsch U,Rossi JF,Goldschmidt H,Klein B

    更新日期:2009-05-07 00:00:00

  • GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment.

    abstract::Recent studies have established that during embryonic development, hematopoietic progenitors and stem cells are generated from hemogenic endothelium precursors through a process termed endothelial to hematopoietic transition (EHT). The transcription factor RUNX1 is essential for this process, but its main downstream e...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-10-386094

    authors: Lancrin C,Mazan M,Stefanska M,Patel R,Lichtinger M,Costa G,Vargel O,Wilson NK,Möröy T,Bonifer C,Göttgens B,Kouskoff V,Lacaud G

    更新日期:2012-07-12 00:00:00