Complement-mediated cell death induced by rituximab in B-cell lymphoproliferative disorders is mediated in vitro by a caspase-independent mechanism involving the generation of reactive oxygen species.

Abstract:

:Mechanisms involving the in vitro effect of rituximab in cells from 55 patients with B-cell lymphoproliferative disorders were investigated. No cytotoxic effect was observed when cells were incubated with rituximab alone, but in the presence of human AB serum rituximab induced complement-dependent cell death (R-CDC). A cytotoxic effect was observed in cells from 9 of 33 patients with B-cell chronic lymphocytic leukemia, 16 of 16 patients with mantle-cell lymphoma, 4 of 4 patients with follicular lymphoma, and 2 of 2 patients with hairy-cell leukemia. R-CDC was observed in cells from patients expressing more than 50 x 10(3) CD20 molecules per cell, and directly correlated with the number of CD20 molecules per cell. Preincubation with anti-CD59 increased the cytotoxic effect of rituximab and sensitized cells from nonsensitive cases. Neither cleavage of poly-ADP ribose polymerase (PARP) nor activation of caspase-3 was observed in R-CDC. In addition, no cells with a hypodiploid DNA content were detected and R-CDC was not prevented by a broad-spectrum caspase inhibitor, suggesting a caspase-independent mechanism. Incubation with rituximab in the presence of AB serum induced a rapid and intense production of reactive oxygen species (ROS). R-CDC was blocked by the incubation of cells with N-acetyl-L-cysteine (NAC) or Tiron, 2 ROS scavengers, indicating that the cytotoxic effect was due to the generation of superoxide (O) radicals. In conclusion, the results of the present study suggest that CD20, CD59, and complement have a role in the in vitro cytotoxic effect of rituximab, which is mediated by a caspase-independent process that involves ROS generation.

journal_name

Blood

journal_title

Blood

authors

Bellosillo B,Villamor N,López-Guillermo A,Marcé S,Esteve J,Campo E,Colomer D,Montserrat E

doi

10.1182/blood.v98.9.2771

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

2771-7

issue

9

eissn

0006-4971

issn

1528-0020

journal_volume

98

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Concomitant granulocyte colony-stimulating factor and induction chemoradiotherapy in adult acute lymphoblastic leukemia: a randomized phase III trial.

    abstract::This prospective multicenter study examined whether simultaneous administration of granulocyte colony-stimulating factor (G-CSF; Filgrastim) and induction chemotherapy for adult acute lymphoblastic leukemia (ALL) could prevent treatment-related neutropenia, infections, and resulting treatment delays. Seventy-six patie...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:

    authors: Ottmann OG,Hoelzer D,Gracien E,Ganser A,Kelly K,Reutzel R,Lipp T,Busch FW,Schwonzen M,Heil G

    更新日期:1995-07-15 00:00:00

  • Characterization and purification of a primitive hematopoietic cell type in adult mouse marrow capable of lymphomyeloid differentiation in long-term marrow "switch" cultures.

    abstract::In this report, we describe a modification of the assay for long-term culture-initiating cells (LTC-IC) that allows a subset of murine LTC-IC (designated as LTC-ICML) to express both their myeloid (M) and lymphoid (L) differentiative potentials in vitro. The modified assay involves culturing test cells at limiting dil...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lemieux ME,Rebel VI,Lansdorp PM,Eaves CJ

    更新日期:1995-08-15 00:00:00

  • Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project.

    abstract::Among 1153 new adult cases of peripheral/T-cell lymphoma from 1990-2002 at 22 centers in 13 countries, 136 cases (11.8%) of extranodal natural killer (NK)/T-cell lymphoma were identified (nasal 68%, extranasal 26%, aggressive/unclassifiable 6%). The disease frequency was higher in Asian than in Western countries and i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-10-185256

    authors: Au WY,Weisenburger DD,Intragumtornchai T,Nakamura S,Kim WS,Sng I,Vose J,Armitage JO,Liang R,International Peripheral T-Cell Lymphoma Project.

    更新日期:2009-04-23 00:00:00

  • Multiple Rh messenger RNA isoforms are produced by alternative splicing.

    abstract::Three Rh-related cDNAs have been isolated from a human bone marrow cDNA library and by polymerase chain reaction (PCR) amplification of human bone marrow and erythroblast mRNAs. They potentially encode a family of Rh protein isoforms that exhibit several unexpected structural properties as compared with the Rh polypep...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Le Van Kim C,Chérif-Zahar B,Raynal V,Mouro I,Lopez M,Cartron JP,Colin Y

    更新日期:1992-08-15 00:00:00

  • Inflammatory cytokines and vascular endothelial growth factor stimulate the release of soluble tie receptor from human endothelial cells via metalloprotease activation.

    abstract::Activation of endothelial cells, important in processes such as angiogenesis, is regulated by cell surface receptors, including those in the tyrosine kinase (RTK) family. Receptor activity, in turn, can be modulated by phosphorylation, turnover, or proteolytic release of a soluble extracellular domain. Previously, we ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Yabkowitz R,Meyer S,Black T,Elliott G,Merewether LA,Yamane HK

    更新日期:1999-03-15 00:00:00

  • Stochastic modeling of human RBC alloimmunization: evidence for a distinct population of immunologic responders.

    abstract::Red blood cell (RBC) transfusion is unique as a common large-scale intravenous introduction of foreign tissue and provides a valuable opportunity to study human immunologic response to intravenous foreign antigen. Patients receiving RBC transfusions are at risk of forming alloantibodies against donor RBC antigens, and...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-03-146415

    authors: Higgins JM,Sloan SR

    更新日期:2008-09-15 00:00:00

  • Exome sequencing identifies recurring FLT3 N676K mutations in core-binding factor leukemia.

    abstract::The t(8;21) and inv(16)/t(16;16) rearrangements affecting the core-binding factors RUNX1 and CBFB, respectively, are found in 15% to 20% of adult de novo acute myeloid leukemia (AML) cases and are associated with a favorable prognosis. Since the expression of the fusion genes CBFB/MYH11 or RUNX1/RUNX1T1 alone is not s...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1182/blood-2013-01-476473

    authors: Opatz S,Polzer H,Herold T,Konstandin NP,Ksienzyk B,Zellmeier E,Vosberg S,Graf A,Krebs S,Blum H,Hopfner KP,Kakadia PM,Schneider S,Dufour A,Braess J,Sauerland MC,Berdel WE,Büchner T,Woermann BJ,Hiddemann W,Spiekerma

    更新日期:2013-09-05 00:00:00

  • Platelet von Willebrand factor: evidence for its involvement in platelet adhesion to collagen.

    abstract::Although it is well established that plasma von Willebrand Factor (vWF) is essential to platelet adhesion to subendothelium at high shear rates, the role of platelet vWF is less clear. We studied the respective role of both plasma and platelet vWF in mediating platelet adhesion to fibrillar collagen in a parallel-plat...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Fressinaud E,Baruch D,Rothschild C,Baumgartner HR,Meyer D

    更新日期:1987-10-01 00:00:00

  • Activation and complexation of protein C and cleavage and decrease of protein S in plasma of patients with intravascular coagulation.

    abstract::Activated protein C (APC) is inhibited by two major plasma inhibitors (PCIs). To find evidence for in vivo complexation of APC, immunoblotting studies were performed on plasmas of 85 patients with suspected disseminated intravascular coagulation (DIC). Samples from 62 of these patients contained 5% to 35% of protein C...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Heeb MJ,Mosher D,Griffin JH

    更新日期:1989-02-01 00:00:00

  • Characterization of the mononuclear phagocyte system in zebrafish.

    abstract::The evolutionarily conserved immune system of the zebrafish (Danio rerio), in combination with its genetic tractability, position it as an excellent model system in which to elucidate the origin and function of vertebrate immune cells. We recently reported the existence of antigen-presenting mononuclear phagocytes in ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-11-321448

    authors: Wittamer V,Bertrand JY,Gutschow PW,Traver D

    更新日期:2011-06-30 00:00:00

  • Studies on the basis for the properties of fibrin produced from fibrinogen-containing gamma' chains.

    abstract::Human fibrinogen 1 is homodimeric with respect to its gamma chains (gammaA-gammaA'), whereas fibrinogen 2 molecules each contain one gammaA (gammaA1-411V) and one gamma' chain, which differ by containing a unique C-terminal sequence from gamma'408 to 427L that binds thrombin and factor XIII. We investigated the struct...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-01-0240

    authors: Siebenlist KR,Mosesson MW,Hernandez I,Bush LA,Di Cera E,Shainoff JR,Di Orio JP,Stojanovic L

    更新日期:2005-10-15 00:00:00

  • A TLR2 ligand suppresses inflammation by modulation of chemokine receptors and redirection of leukocyte migration.

    abstract::Toll-like receptors orchestrate rapid local protective innate-immune responses to invading pathogens and optimize leukocyte priming of subsequent adaptive responses. Paradoxically, systemic excess of the TLR2 ligand, bacterial lipoprotein (BLP), suppresses peripheral inflammatory responses. Here, we demonstrate that t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-08-174698

    authors: McKimmie CS,Moore M,Fraser AR,Jamieson T,Xu D,Burt C,Pitman NI,Nibbs RJ,McInnes IB,Liew FY,Graham GJ

    更新日期:2009-04-30 00:00:00

  • VEGF(165) promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition.

    abstract::Similar to endothelial cells (ECs), vascular endothelial growth factor (VEGF) induces Bcl-2 expression on VEGF receptor-positive (VEGFR(+)) primary leukemias and cell lines, promoting survival. We investigated the molecular pathways activated by VEGF on such leukemias, by performing a gene expression analysis of VEGF-...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.7.2532

    authors: Dias S,Shmelkov SV,Lam G,Rafii S

    更新日期:2002-04-01 00:00:00

  • Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia-induced apoptosis.

    abstract::Neuroserpin, a recently identified inhibitor of tissue-type plasminogen activator (tPA), is primarily localized to neurons within the central nervous system, where it is thought to regulate tPA activity. In the present study neuroserpin expression and its potential therapeutic benefits were examined in a rat model of ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Yepes M,Sandkvist M,Wong MK,Coleman TA,Smith E,Cohan SL,Lawrence DA

    更新日期:2000-07-15 00:00:00

  • Stimulation of neutrophil oxidative metabolism by the alternate pathway of complement activation: a mechanism for the spontaneous NBT test.

    abstract::The reduction of nitroblue tetrazolium dye by human neutrophils was measured in the presence of serum in which the complement system had been activated through the alternate pathway by interaction with inulin. Neutrophils incubated with serum inulin supernatants reduced the dye and showed a general increase in oxidati...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Strauss RG,Mauer AM,Asbrock T,Spitzer RE,Stitzel AE

    更新日期:1975-06-01 00:00:00

  • Isotype switch variants reveal clonally related subpopulations in diffuse large B-cell lymphoma.

    abstract::Primary diffuse large B-cell lymphomas (DLBCLs) are aggressive tumors accounting for approximately 40% of B-cell malignancies. The immunoglobulin (Ig) variable region genes have undergone rearrangement and are commonly somatically mutated. The majority show intraclonal variation which indicates that somatic mutation h...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ottensmeier CH,Stevenson FK

    更新日期:2000-10-01 00:00:00

  • Intracellular storage and regulated plasma membrane expression of human complement receptor type 1 in rat basophil leukemia cell transfectants.

    abstract::Polymorphonuclear neutrophils (PMN) contain multiple distinct secretory compartments that are sequentially mobilized during cell activation. Complement receptor type 1 (CR1) is a marker for a readily mobilizable secretory vesicle compartment, which can undergo exocytic fusion with the plasma membrane independently of ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Jost C,Klickstein L,Wetzler E,Kumar A,Berger M

    更新日期:1998-07-01 00:00:00

  • Effects of neuraminidase on the regulation of erythropoiesis.

    abstract::In this article, we present evidence that sialic acid-containing surface components play a role in the regulation of erythropoiesis. A 1-hr exposure of mouse bone marrow cells to high concentrations of neuraminidase reduced erythroid colony formation. Coculture of 10(6) untreated thymocytes with neuraminidase-treated ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: LaRussa VF,Sieber F,Sensenbrenner LL,Sharkis SJ

    更新日期:1984-04-01 00:00:00

  • Dynamics of complement activation in aHUS and how to monitor eculizumab therapy.

    abstract::Atypical hemolytic-uremic syndrome (aHUS) is associated with genetic complement abnormalities/anti-complement factor H antibodies, which paved the way to treatment with eculizumab. We studied 44 aHUS patients and their relatives to (1) test new assays of complement activation, (2) verify whether such abnormality occur...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2014-02-558296

    authors: Noris M,Galbusera M,Gastoldi S,Macor P,Banterla F,Bresin E,Tripodo C,Bettoni S,Donadelli R,Valoti E,Tedesco F,Amore A,Coppo R,Ruggenenti P,Gotti E,Remuzzi G

    更新日期:2014-09-11 00:00:00

  • Pediatric acute lymphoblastic leukemia: where are we going and how do we get there?

    abstract::Improved supportive care, more precise risk stratification, and personalized chemotherapy based on the characteristics of leukemic cells and hosts (eg, pharmacokinetics and pharmacogenetics) have pushed the cure rate of childhood acute lymphoblastic leukemia to near 90%. Further increase in cure rate can be expected f...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2012-05-378943

    authors: Pui CH,Mullighan CG,Evans WE,Relling MV

    更新日期:2012-08-09 00:00:00

  • R93W mutation in Orai1 causes impaired calcium influx in platelets.

    abstract::The intracellular Ca(2+) concentration of many nonexcitable cells is regulated by calcium store release and store-operated calcium entry (SOCE). In platelets, STIM1 was recently identified as the main calcium sensor expressed in the endoplasmic reticulum. To evaluate the role of the SOC channel moiety, Orai1, in plate...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-08-174516

    authors: Bergmeier W,Oh-Hora M,McCarl CA,Roden RC,Bray PF,Feske S

    更新日期:2009-01-15 00:00:00

  • Ultrastructural localization of nonspecific esterase activity in guinea pig and human monocytes, macrophages, and lymphocytes.

    abstract::Using either hexazotized pararosaniline or new fuchsin as coupling agents, we investigated the ultrastructural localization of alpha-naphthyl acetate esterase (ANAE) activity in guinea pig bone marrow and peritoneal exudates, and in human peripheral blood cells. DFP-inhibitable ANAE activity was present on the cell su...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Monahan RA,Dvorak HF,Dvorak AM

    更新日期:1981-12-01 00:00:00

  • A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells.

    abstract::Adaptive immunity is triggered at the immune synapse, where peptide-major histocompatibility complexes and costimulatory molecules expressed by dendritic cells (DCs) are physically presented to T cells. Here we describe transmission of the inflammatory monoamine serotonin (5-hydroxytryptamine [5-HT]) between these cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-07-2903

    authors: O'Connell PJ,Wang X,Leon-Ponte M,Griffiths C,Pingle SC,Ahern GP

    更新日期:2006-02-01 00:00:00

  • A unique 7p/12q chromosomal abnormality associated with recurrent abortion and hypofibrinogenemia.

    abstract::Recurrent first trimester abortions led to evaluation of a 25-year-old woman. Studies revealed she had hypofibrinogenemia (68 mg/dL) without evidence of dysfibrinogenemia or increased fibrinogen turnover. She was also found to have a unique 46,XX, t(7;12) (p 15.2;q24.31) karyotype. Hypofibrinogenemia and identical chr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kitchens CS,Cruz AC,Kant JA

    更新日期:1987-10-01 00:00:00

  • An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B ligand.

    abstract::Identification of receptor activator of nuclear factor-kappaB (RANK) and RANK-ligand (RANKL) has provided new insights into the osteoclast differentiation pathway. Osteoclast precursor cells were isolated using monoclonal antibodies against c-Fms and RANK, and the effect of adherence on the in vitro differentiation an...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Miyamoto T,Arai F,Ohneda O,Takagi K,Anderson DM,Suda T

    更新日期:2000-12-15 00:00:00

  • Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response.

    abstract::Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognized variability in clinical outcome, genetic features, and cells of origin. To date, transcriptional profiling has been used to highlight similarities between DLBCL tumor cells and normal B-cell subtypes and associate genes and pathways with ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-07-2947

    authors: Monti S,Savage KJ,Kutok JL,Feuerhake F,Kurtin P,Mihm M,Wu B,Pasqualucci L,Neuberg D,Aguiar RC,Dal Cin P,Ladd C,Pinkus GS,Salles G,Harris NL,Dalla-Favera R,Habermann TM,Aster JC,Golub TR,Shipp MA

    更新日期:2005-03-01 00:00:00

  • The inflammatory action of CD40 ligand (CD154) expressed on activated human platelets is temporally limited by coexpressed CD40.

    abstract::Recently, we have demonstrated that human platelets carry preformed CD40 ligand (CD154) molecules, which rapidly appear on the platelet surface following stimulation by thrombin. Once on the surface, platelet CD154 induces an inflammatory reaction of CD40-bearing endothelial cells. This study shows that strong platele...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.4.1047

    authors: Henn V,Steinbach S,Büchner K,Presek P,Kroczek RA

    更新日期:2001-08-15 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

  • Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification.

    abstract::Multisystem Langerhans cell histiocytosis (MS-LCH) is associated with high mortality when patients have risk organ involvement (RO(+)) or are younger than 2 years. In an international randomized trial, LCH-II, we intensified their treatment: arm A consisted of 6 weeks of daily prednisone and weekly vinblastine followe...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2007-08-106211

    authors: Gadner H,Grois N,Pötschger U,Minkov M,Aricò M,Braier J,Broadbent V,Donadieu J,Henter JI,McCarter R,Ladisch S,Histiocyte Society.

    更新日期:2008-03-01 00:00:00

  • Human regulatory T cells in allogeneic stem cell transplantation.

    abstract::GVHD is still one of the major complications after allogeneic stem cell transplantation. Whereas murine data have clearly shown the beneficial effects of regulatory T cells (Tregs) on the prevention of GVHD, data from the human system are rare. Here, we present a comparative dynamic analysis of CD4(+)CD25(hi)CD127(lo/...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-05-352708

    authors: Ukena SN,Velaga S,Geffers R,Grosse J,Baron U,Buchholz S,Stadler M,Bruder D,Ganser A,Franzke A

    更新日期:2011-09-29 00:00:00