Abstract:
:Deleted in malignant brain tumors 1 (DMBT1) is a secreted glycoprotein displaying a broad bacterial-binding spectrum. Recent functional and genetic studies linked DMBT1 to the suppression of LPS-induced TLR4-mediated NF-kappaB activation and to the pathogenesis of Crohn's disease. Here, we aimed at unraveling the molecular basis of its function in mucosal protection and of its broad pathogen-binding specificity. We report that DMBT1 directly interacts with dextran sulfate sodium (DSS) and carrageenan, a structurally similar sulfated polysaccharide, which is used as a texturizer and thickener in human dietary products. However, binding of DMBT1 does not reduce the cytotoxic effects of these agents to intestinal epithelial cells in vitro. DSS and carrageenan compete for DMBT1-mediated bacterial aggregation via interaction with its bacterial-recognition motif. Competition and ELISA studies identify poly-sulfated and poly-phosphorylated structures as ligands for this recognition motif, such as heparansulfate, LPS, and lipoteichoic acid. Dose-response studies in Dmbt1(-/-) and Dmbt1(+/+) mice utilizing the DSS-induced colitis model demonstrate a differential response only to low but not to high DSS doses. We propose that DMBT1 functions as pattern-recognition molecule for poly-sulfated and poly-phosphorylated ligands providing a molecular basis for its broad bacterial-binding specificity and its inhibitory effects on LPS-induced TLR4-mediated NF-kappaB activation.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
End C,Bikker F,Renner M,Bergmann G,Lyer S,Blaich S,Hudler M,Helmke B,Gassler N,Autschbach F,Ligtenberg AJ,Benner A,Holmskov U,Schirmacher P,Nieuw Amerongen AV,Rosenstiel P,Sina C,Franke A,Hafner M,Kioschis P,Schredoi
10.1002/eji.200838689subject
Has Abstractpub_date
2009-03-01 00:00:00pages
833-42issue
3eissn
0014-2980issn
1521-4141journal_volume
39pub_type
杂志文章abstract::Strains CBA (M523) (= M523) and CBA differ by a mutation which has been mapped genetically into the K region of the H-2 complex. Similarly, strains B 10.D2 (M504 (= M504) and b 10.D2 differ in a mutation which occurred in the D region. The data presented in this study show that mixed lymphocyte culture in M523 anti-CB...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830090208
更新日期:1979-02-01 00:00:00
abstract::The molecular mimicry represented by cross-recognition of determinants shared by unrelated antigens by antibodies or T cells is of broad immunological interest. In this study, we analyzed the cross-recognition by CD4+ T cells of a peptide epitope shared by two mycobacterial proteins of diverse sequence, represented by...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830251128
更新日期:1995-11-01 00:00:00
abstract::Changes in the epigenetic landscape of immune cells are a crucial component of gene activation during the induction of inflammatory responses, therefore it has been hypothesized that epigenetic modulation could be employed to restore homeostasis in inflammatory scenarios. Fungal pathogens cause a large burden of morbi...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201848081
更新日期:2019-11-01 00:00:00
abstract::The stimulatory as well as the inhibitory capacity of alloantisera has been investigated with respect to rat mast cell functions. Alloantibody against alloantigens coded for by the major histocompatibility (H-1) gene region promoted histamine release from purified LEW mast cells. This process was found to be complemen...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830060813
更新日期:1976-08-01 00:00:00
abstract::The human promyelocytic U937 cells express detectable levels of MHC class II (MHC-II) molecules. Treatment with 12-o--tetradecanoyl phorbol 13-acetate (TPA), inducing macrophage-like differentiation, produces a dramatic decrease of MHC-II expression as result of down-modulation of the activation of immune response gen...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200425378
更新日期:2005-02-01 00:00:00
abstract::The conditions under which tumor necrosis factor-alpha (TNF) induces apoptosis in primary microvascular endothelial cells (MVEC) were investigated. In the absence of sensitizing agents, TNF induced apoptosis after 3 days of incubation in confluent MVEC. In contrast, upon addition of the transcriptional inhibitor actin...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199811)28:11<3577::AID-IMM
更新日期:1998-11-01 00:00:00
abstract::CD4+CD25(hi)CD127(lo/-) regulatory T cells (Treg) have been implicated in the resolution of asthma-associated inflammation while the opposite role of CD4+ invariant NKT (iNKT) cells has been the subject of recent investigations. Studies here focused on mechanisms of interaction between CD4+ iNKT cells and Treg to furt...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200738082
更新日期:2008-07-01 00:00:00
abstract::Endogenous superantigens (SAg) presented by MHC class II IA molecules induce slow-evolving negative selection of alpha beta T cells. The role of both B and gamma delta T cells on the regulation of these SAg-specific alpha beta T cell responses was addressed in IA(b+)IE(b-) C57BL/6 mice bearing genetically induced B ce...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200109)31:9<2811::aid-immu2811>3
更新日期:2001-09-01 00:00:00
abstract::To investigate the role of interferon-gamma (IFN-gamma) in experimental autoimmune thyroidits (EAT), H-2k mice with a disrupted IFN-gamma receptor (IFN-gamma R) gene were immunized with porcine thyroglobulin (pTg). We observed that EAT occurred on day 19 and remitted on day 35 in IFN-gamma R-deficient (IFN-gamma R(0/0...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199801)28:01<201::AID-IMMU
更新日期:1998-01-01 00:00:00
abstract::After incorporation of 14C-labeled amino acids and/or of [3H]fucose during in vitro culture of the Thy-1.1-bearing, Fc receptor-positive T lymphoma, L-5187-Y, attempts were made to purify the Fc binding structure(s). Following solubilization of a crude membrane pellet using sodium deoxycholate, the 110 000 x g superna...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830070916
更新日期:1977-09-01 00:00:00
abstract::MHC-peptide-specific Fab antibodies binding to HLA-A*0201 complexes presenting the wild-type EAAGIGILTV (EAA) or analogue Melan-A 10-mer ELAGIGILTV (ELA) peptide were generated to study efficacy of peptide processing and presentation. None of the selected Fab antibodies detected the naturally processed EAA/HLA-A*0201 ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200636545
更新日期:2007-07-01 00:00:00
abstract::We studied the competitive repopulation by different B cells of irradiated mice reconstituted with bone marrow from either congenic or Ig-transgenic (TG) mice mixed at different ratios. We found that after reconstitution, the number of B cells recovered in the different chimeras is similar and independent of the ratio...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250636
更新日期:1995-06-01 00:00:00
abstract::Interferon-gamma inducing factor (IGIF) is a recently identified cytokine which stimulates the production of interferon-gamma (IFN-gamma) by T cells and enhances natural killer (NK) cell cytolytic activity. Protein fold recognition, structure prediction and comparative modeling have revealed that IGIF is a member of t...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830271107
更新日期:1997-11-01 00:00:00
abstract::Toll-like receptors (TLR) 7 and 8 are closely related members of the TLR family of pathogen-associated molecular pattern recognition receptors and have an important function in activation of innate immune responses upon viral infection. TLR7 can be activated selectively by the guanosine analogue loxoribine, whereas th...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200535806
更新日期:2006-07-01 00:00:00
abstract::CD4+ CD25+ Foxp3+ regulatory T cells (Treg) are natural suppressors of autoimmunity but they can also dampen the effective clearance of infectious organisms. These cells have the potential to be exploited to prevent transplant rejection and to treat autoimmune disease. A paper in this issue of the European Journal of ...
journal_title:European journal of immunology
pub_type: 评论,杂志文章,评审
doi:10.1002/eji.200635967
更新日期:2006-04-01 00:00:00
abstract::We have explored how IL-15 influences Th1 or Th2 type immune response in vivo. Intraperitoneal application of an IL-15-IgG2b fusion protein (FP) to mice did neither significantly affect the footpad swelling nor the production of hemagglutinizing antibodies in a delayed type hypersensitivity reaction to sheep red blood...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199810)28:10<3312::AID-IMM
更新日期:1998-10-01 00:00:00
abstract::DC not only activate CD4 T (Th) cell and cytotoxic CD8 T cell (CTL) responses against pathogens, but they also tolerize autoreactive T cells in order to avoid autoimmunity. Previous studies have demonstrated that steady-state DC can tolerize naïve CTL, naïve Th cells and memory CTL. A study in this issue of the Europe...
journal_title:European journal of immunology
pub_type:
doi:10.1002/eji.201040704
更新日期:2010-07-01 00:00:00
abstract::The objective of the present investigation was to culture helper or suppressor/cytotoxic T cell subsets after extensive purification in interleukin 2-containing medium to determine whether phenotype changes for OKT4/91d6- or OKT8/Leu-2a-defined antigens do occur with prolonged culture. Repeated and sequential analysis...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830140819
更新日期:1984-08-01 00:00:00
abstract::A hallmark of parasite infection is the accumulation of innate immune cells, notably granulocytes and mast cells, at the site of infection. While this is typically viewed as a transient response, with the tissue returning to steady state once the infection is cleared, we found that mast cells accumulated in the large-...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201646738
更新日期:2017-02-01 00:00:00
abstract::Recurrent respiratory tract infections (RRTIs) are the first leading cause of community- and nosocomial-acquired infections. Antibiotics remain the mainstay of treatment, enhancing the potential to develop antibiotic resistances. Therefore, the development of new alternative approaches to prevent and treat RRTIs is hi...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201747024
更新日期:2018-01-01 00:00:00
abstract::The present study demonstrates that the C3b receptor CR1 (CD35) and the C3dg/Epstein-Barr virus receptor CR2 (CD21) are expressed by 25% and 70% of normal human thymocytes, respectively. The expression of CR2 extends to both CD1+ and CD1- cells in the thymus. Two subsets of CR2+ thymocytes were defined expressing low ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830241131
更新日期:1994-11-01 00:00:00
abstract::LIGHT is a recently identified member of the TNF superfamily that is up-regulated on activated T cells and can cooperate with CD40L to condition DC for the priming of CTL. In this report, we show that an intracellular pool of LIGHT is found selectively in some CD45RA-CD27+CD4+ "central" memory T cells and to a greater...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200324410
更新日期:2003-11-01 00:00:00
abstract::Two different lines of C57BL/6 mice (IgHb) carrying complete rearranged mu chain genes from BALB/c (IgMa) were analyzed for the expression and secretion of endogenous as well as transgenic immunoglobulins at the level of single cells. Quantitation of B cells expressing endogenous IgMb by cytofluorometry, limiting dilu...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830200507
更新日期:1990-05-01 00:00:00
abstract::Interphotoreceptor retinoid-binding protein (IRBP) is an immunologically privileged retinal antigen that can elicit experimental autoimmune uveitis (EAU). The nature and extent of tolerance to immunologically privileged self antigens is poorly understood. To investigate whether transgenic expression of IRBP extraocula...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200001)30:1<272::AID-IMMU272>3.0
更新日期:2000-01-01 00:00:00
abstract::B cells in rabbit preferentially utilize the 3'-most VH gene, VH1, in VDJ genes. To determine whether the preferential utilization of VH1 results from preferential rearrangement, we examined VH gene usage in nonproductive VDJ gene rearrangements, genes that would not be influenced by antigen selection. Since nonproduc...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250927
更新日期:1995-09-01 00:00:00
abstract::A panel of closely and distantly related lysozymes and lysozyme-peptide fragments were utilized in assessing the specificity repertoire of murine anti-hen egg white lysozyme hybridomas. The 44 monoclonal antibodies could be divided into a minimum of 18 fine specificity groups in tests using the lysozyme panel. Two hyb...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830140116
更新日期:1984-01-01 00:00:00
abstract::The tight-skin (Tsk/+) mutant mouse, a putative murine model of scleroderma, is characterized primarily by the excessive deposition of collagen and other extracellular matrix molecules in the dermis, and also by a developmentally acquired defect in pulmonary architecture. Passive transfer experiments have suggested an...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199809)28:09<2619::AID-IMM
更新日期:1998-09-01 00:00:00
abstract::Stimulation of T cells via the T cell receptor (TCR) leads to an increase intracellular in free Ca2+ levels ([Ca2+]i) and the activation of the MAP kinase signaling pathway. This study analyzes for the first time Ca2+ fluxes in naive cytotoxic T cells stimulated with full agonists, partial agonists, or antagonists. Fo...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830271241
更新日期:1997-12-01 00:00:00
abstract::Rabbit kappa light (L) chain allotypes are controlled by the allelic genes b4, b5, b6, b9 and a recently described allele b4v. The product of the b4v gene differs from that of b4 by at least two amino acid substitutions in the constant region. A serologic distinction between the b4 and b4v allotyes has now been detect...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830090107
更新日期:1979-01-01 00:00:00
abstract::The development of preventive or therapeutic recombinant vaccines and the generation of serodiagnostic assays for infectious diseases depend essentially on the availability of molecularly defined antigens. A major bottleneck for the identification of suitable target antigens for many pathogens is the isolation of suff...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200535538
更新日期:2006-04-01 00:00:00