Abstract:
:Autoantibodies characteristic for anti-phospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are anti-β2 -glycoprotein I (β2 GPI) antibodies and anti-DNA antibodies, respectively, and almost half of APS cases occur in SLE. Anti-β2 GPI antibodies are recognized to play a pivotal role in inducing a prothrombotic state, but the precise mechanism has not been fully elucidated. In a widely accepted view, binding of anti-β2 GPI antibodies to cell surface β2 GPI in monocytes and endothelial cells triggers the Toll-like receptor 4-myeloid differentiation primary response 88 (TLR)-4-MyD88) signaling pathway which leads to activation of p38 mitogen-activated protein kinase (MAPK), mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinases (MEK-1/ERK) and/or nuclear factor kappa B (NF-κB) and expression of tissue factor (TF). However, resting cells do not express substantial amounts of TLR-4. Previously, we generated a mouse monoclonal anti-β2 GPI antibody WB-6 and showed that it induced a prothrombotic state - including TF expression on circulating monocytes - in normal mice. In the current study, we aimed to clarify the mechanism of interaction between WB-6 and resting monocytes, and found that WB-6 exhibits binding activity to DNA and enters living monocytes or a monocytic cell line and, to a lesser extent, vascular endothelial cells. Treatment of the cells with DNase I reduced the internalization, suggesting the involvement of cell surface DNA in this phenomenon. Monocytes harboring internalized WB-6 expressed TF and tumor necrosis factor (TNF)-α which, in turn, stimulated endothelial cells to express intercellular adhesion molecule 1 (ICAM-I) and vascular cell adhesion molecule 1 (VCAM-I). These results suggest the possibility that a subset of anti-β2 GPI antibodies with dual reactivity to DNA possesses ability to stimulate DNA sensors in the cytoplasm, in addition to the cell surface receptor-mediated pathways, leading to produce proinflammatory and prothrombotic states.
journal_name
Clin Exp Immunoljournal_title
Clinical and experimental immunologyauthors
Virachith S,Saito M,Watanabe Y,Inoue K,Hoshi O,Kubota Tdoi
10.1111/cei.13229subject
Has Abstractpub_date
2019-02-01 00:00:00pages
167-178issue
2eissn
0009-9104issn
1365-2249journal_volume
195pub_type
杂志文章abstract::In order to study the role of gamma/delta T cells in the pathogenesis of inflammatory bowel disease (IBD) in humans, we measured the percentage of these cells in the peripheral blood, assessed the ratio of the non-disulphide-linked (delta TCS1) type of T cell receptor (TCR) in the total gamma/delta T cells, studied th...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1994.tb06611.x
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abstract::Macrophages play a central role in inflammation and host defence against microorganisms, but they also participate actively in the resolution of inflammation after alternative activation. However, it is not known whether the resolution of inflammation requires alternative activation of new resting monocytes/macrophage...
journal_title:Clinical and experimental immunology
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abstract::It has been demonstrated immunohistologically using cryostat sections that the lectins PHA and Con A bind to human placentae. Both lectins stain trophoblastic basement membrane (TBM), perivascular tissue and stroma. No staining of trophoblasts was observed. It has been shown by blocking experiments that the lectin bin...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1976-06-01 00:00:00
abstract::It has been postulated that IgA nephropathy (IgAGN) is caused by deposition within the glomerular mesangium of IgA polymers and IgA containing immune complexes which are overproduced in response to antigens presented at mucosal surfaces. To test this, the concentrations of specific antibodies to capsular polysaccharid...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::Sixteen healthy adults had serial studies of delayed-type skin test reactivity and in vitro lymphocyte blastogenesis to several antigens over a period of 7 months. In many subjects blastogenesis varied broadly from month to month without apparent cause. Responses to all antigens usually increased or decreased together...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1976-07-01 00:00:00
abstract::Delayed-type hypersensitivity (DTH) to a soluble Mycobacterium leprae skin test antigen (SML) was successfully induced in healthy volunteers following immunization with 2 X 10(8) killed armadillo-derived M. leprae. No better sensitization was obtained by a mixture of live BCG and killed M. leprae. The relative specifi...
journal_title:Clinical and experimental immunology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1981-06-01 00:00:00
abstract::Macaques provide important animal models in biomedical research into infectious and chronic inflammatory disease. Therefore, a proper understanding of the similarities and differences in immune function between macaques and humans is needed for adequate interpretation of the data and translation to the human situation...
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
abstract::The number of thymic epithelial cells containing the serum thymic factor (FTS or thymulin), assessed by indirect immunofluorescence using an anti-FTS monoclonal antibody, was studied in the thymus of normal and autoimmune mice as a function of age. In normal mice the number of FTS+ cells was constant until the age of ...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1983-04-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1979-04-01 00:00:00
abstract::Serum from 98 Thai adults infected with Plasmodium falciparum were examined for the presence of autoantibodies. Malarial containing antibodies sera were also revealed positive for anti-nuclear antibodies with fluorescence speckled pattern, anti-smooth muscle antibodies, anti-mitochondria antibodies and rheumatoid fact...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1984-10-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/cei.13509
更新日期:2020-12-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1978-03-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.1990.tb03310.x
更新日期:1990-06-01 00:00:00
abstract::Nickel (Ni), the main cause of contact allergy to metals, induces in vitro production of both Th1- and Th2-type cytokines in peripheral blood mononuclear cells (PBMC) from allergic subjects. Because the knowledge of the cellular immune response to other metals involved in contact allergy has been limited, we investiga...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2249.2006.03226.x
更新日期:2006-12-01 00:00:00
abstract::Antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood lymphocytes against chicken red blood cells (ChRBC) in the presence of specific antiserum has been studied in normal subjects and in patients with acute hepatitis B and with chronic active hepatitis (CAH). ADCC was significantly reduced in patients wi...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1978-08-01 00:00:00
abstract::We report a case of a combined immunodeficiency (CID) in a child affected by trichothiodystrophy (TTD) characterized by an altered response to ultraviolet (UV) light due to a defect in the XPD gene. The XPD gene encodes a subunit of the transcription factor II H (TFIIH), a complex involved in nucleotide-excision repai...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2249.2001.01625.x
更新日期:2001-12-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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pub_type: 临床试验,杂志文章
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1985-04-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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更新日期:2019-07-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1988-04-01 00:00:00
abstract::A solid-phase radioimmunoassay was developed to detect antibodies to liver membrane antigens in sera of patients with HBsAg-negative and -positive liver diseases and primary non-hepatic autoimmune diseases. Ten of fourteen patients with HBsAg-negative CAH had autoantibodies detected by RIA; negative results were obtai...
journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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更新日期:2004-05-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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更新日期:1991-04-01 00:00:00