更新于：2024-11-01

CD3 x Chondroitin sulfate proteoglycans

更新于：2024-11-01

基本信息

关联

项与 CD3 x Chondroitin sulfate proteoglycans 相关的药物

CSPG4-X-CD3

靶点

CD3 x Chondroitin sulfate proteoglycans

作用机制

CD3抑制剂 [+1]

在研机构-

原研机构

Biotecnol Ltd.初创企业

在研适应症-

非在研适应症

肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

CSPG4-CSPG4-CD3

靶点

CD3 x Chondroitin sulfate proteoglycans

作用机制

CD3抑制剂 [+1]

在研机构-

原研机构

Biotecnol Ltd.初创企业

在研适应症-

非在研适应症

肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CD3 x Chondroitin sulfate proteoglycans 相关的临床结果

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100 项与 CD3 x Chondroitin sulfate proteoglycans 相关的转化医学

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0 项与 CD3 x Chondroitin sulfate proteoglycans 相关的专利（医药）

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项与 CD3 x Chondroitin sulfate proteoglycans 相关的文献（医药）

1998-11-01·European Journal of Immunology3区 · 医学

Lymphocyte-specific chemokine receptor CXCR3: regulation, chemokine binding and gene localization

3区 · 医学

Article

作者: Pius Loetscher ; Marcel Loetscher ; Eckart Meese ; Nicole Brass ; Bernhard Moser

Expression of CXCR3, the receptor for the CXC chemokines IFN-gamma-inducible 10-kDa protein (IP10) and monokine induced by IFN-gamma (Mig), in human T lymphocytes and their responses to IP10 and Mig were analyzed. About 40 % of resting T lymphocytes (and low numbers of B cells and natural killer cells) stained positive for CXCR3 but these cells did not express CXCR3 transcripts and did not respond to these chemokines. However, treatment with IL-2 with or without addition of phytohemagglutinin for 10 or more days resulted in cultures of fully responsive, CXCR3-positive T lymphocytes. Treatment with anti-CD3 antibodies in the presence or absence of soluble anti-CD28 antibodies was inhibitory. Addition of chondroitin sulfate C to CXCR3-expressing murine pre-B cells allowed the determination of high-affinity binding for Mig and IP10 with Kd of 0.9-1.2 nM and 0.2-0.3 nM, respectively, and 1.3 x 10(4) binding sites per cell. The gene for CXCR3 was localized on human chromosome Xq13 which is in clear contrast to all other chemokine receptor genes, suggesting unique function(s) for this receptor and its ligands that may lie beyond their established role in T cell-dependent immunity.

1990-12-01·Biochemistry3区 · 生物学

Interaction of chondroitin sulfate with perforin and granzymes of cytolytic T-cells is dependent on pH

3区 · 生物学

Article

作者: Peters, Peter J. ; Borst, Jannie ; Masson, Daniele ; Geuze, Hans J. ; Tschopp, Juerg

Cytolytic T-lymphocytes (CTL) harbor cytoplasmic granules containing the lytic, pore-forming protein perforin, a family of serine proteases designated granzymes, and proteoglycans as major constituents. Growth of CTL lines in the presence of PNP-xyloside completely inhibited the glycosylation of the granule-associated chondroitin sulfate A type proteoglycans. Only short glycosaminoglycan molecules were detected. The absence of intact proteoglycans neither altered the sorting of the granule-associated proteins perforin or granzyme A nor influenced their secretion into the extracellular milieu upon T-cell receptor complex stimulation. With a weak base, the pH of the granules was determined to be acidic. At pH 5.2, granzyme A and perforin formed complexes with chondroitin sulfate A. At neutral pH, perforin and only a minor fraction of granzyme A dissociated from the proteoglycan. Upon secretion of the granule contents induced by immobilized anti-CD3 antibodies, most granzyme A molecules remained complexed with the chondroitin sulfate A glycosaminoglycans, even if synthesis of intact proteoglycans was inhibited. We suggest that granule-associated molecules complex with proteoglycans under the acidic conditions prevailing in the trans Golgi and cytolytic granules. A possible pH shift occurring during exocytosis would cause perforin, but only a minor fraction of granzyme A, to dissociate from the proteoglycans.

Frontiers in Aging Neuroscience2区 · 医学

Acute TBK1/IKK-ε Inhibition Enhances the Generation of Disease-Associated Microglia-Like Phenotype Upon Cortical Stab-Wound Injury

2区 · 医学

ArticleOA

作者: Tar, Lilla ; Ludolph, Albert ; Li, Zhenghui ; Wiesner, Diana ; Roselli, Francesco ; Weishaupt, Jochen ; Kassubek, Jan ; Rehman, Rida ; Olamide, Adeyemi Jubril ; Böckers, Tobias

Traumatic brain injury has a poorer prognosis in elderly patients, possibly because of the enhanced inflammatory response characteristic of advanced age, known as “inflammaging.” Recently, reduced activation of the TANK-Binding-Kinase 1 (Tbk1) pathway has been linked to age-associated neurodegeneration and neuroinflammation. Here we investigated how the blockade of Tbk1 and of the closely related IKK-ε by the small molecule Amlexanox could modify the microglial and immune response to cortical stab-wound injury in mice. We demonstrated that Tbk1/IKK-ε inhibition resulted in a massive expansion of microglial cells characterized by the TMEM119+/CD11c+ phenotype, expressing high levels of CD68 and CD317, and with the upregulation of Cst7a, Prgn and Ccl4 and the decrease in the expression levels of Tmem119 itself and P2yr12, thus a profile close to Disease-Associated Microglia (DAM, a subset of reactive microglia abundant in Alzheimer’s Disease and other neurodegenerative conditions). Furthermore, Tbk1/IKK-ε inhibition increased the infiltration of CD3+ lymphocytes, CD169+ macrophages and CD11c+/CD169+ cells. The enhanced immune response was associated with increased expression of Il-33, Ifn-g, Il-17, and Il-19. This upsurge in the response to the stab wound was associated with the expanded astroglial scars and increased deposition of chondroitin-sulfate proteoglycans at 7 days post injury. Thus, Tbk1/IKK-ε blockade results in a massive expansion of microglial cells with a phenotype resembling DAM and with the substantial enhancement of neuroinflammatory responses. In this context, the induction of DAM is associated with a detrimental outcome such as larger injury-related glial scars. Thus, the Tbk1/IKK-ε pathway is critical to repress neuroinflammation upon stab-wound injury and Tbk1/IKK-ε inhibitors may provide an innovative approach to investigate the consequences of DAM induction.