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CRI (CD35) As a Cellular Receptor for CIq

CRI (CD35) 作为 CIq 的细胞受体

基本信息

批准号：
7191597
负责人：
ANNE NICHOLSON-WELLER
金额：
$ 45.01万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-30 至 2008-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7191597
关键词：
Adaptor Signaling Protein Amino Acid Substitution Apoptotic Attention Autoantigens Autoimmune Diseases Autoimmunity B Cell Proliferation B-Lymphocytes Binding Binding Proteins Binding Sites Biology C3bi Cell surface Cells Characteristics Collagen Complement Complement 1q Complement 3b Complement 3d Receptors Complement 4b Complement Receptor Complex Condition Cytoplasmic Tail Deposition Down-Regulation Employee Strikes Epitope Mapping Exanthema Goals Grant Hematopoietic Homologous Protein Human Immune response Investigation Laboratories Lectin Receptors Leukocytes Ligand Binding Ligands Ligation Link Lupus Macrophage-1 Antigen Mannose Binding Lectin Maps Mediating Microtubules Modification Mono-S Monoclonal Antibodies Monozygotic twins Morbidity - disease rate Natural Immunity Necrosis Nephritis Normal Cell Numbers Pathogenesis Pathway interactions Patients Phagocytes Phagocytosis Phenotype Prevention Process Proteins Recombinant Proteins Recombinants Recruitment Activity Relative (related person)Research Personnel Rest Risk Rodent Role Signal Pathway Signal Transduction Surface Syndrome Testing Tissues calreticulin complement C3d,g complement C4d early onset immunogenic insight lymphoblastoid cell line macrophage monocyte mortality novel prevent programs protein function receptor receptor binding serine esterase uptake

项目摘要

DESCRIPTION (provided by applicant): Clq and MBL participate in tissue remodeling by tagging apoptotic and necrotic tissue, respectively. Clq deficiency is associated with a 93% chance of developing a lupus-like syndrome characterized by an early onset of severe rash and nephritis with high morbidity and mortality. This striking association indicates an important role for Clq in the prevention of autoimmunity, which must depend upon interactions with Clq receptors, since the phenotypes of C4 and C2 deficiencies are much less severe. Our laboratories have demonstrated that Clq and MBL bind specifically to complement receptor 1 (CD35) on hematopoietic cells. Two hypotheses are proposed to link Clq deficiency and autoimmunity. First, Clq-dependent ligation of CD35 on B cells may evoke a negative signal that inhibits B cell proliferation. Second, Clq-dependent opsonization of apoptotic material and clearance by a CD35+ phagocyte prevents autoantigens from becoming immunogenic. The three aims of this proposal are: (1) To determine more precisely the binding site on CD35 for Clq and the binding site on Clq for CD35. (2) To define the functional consequences of Clq ligation of CD35 on leukocytes including the relevant signaling pathway utilized by CD35 on B cells and phagocytic cells. (3) To evaluate the ability of Clq-opsonized apoptotic material to be ingested via a CD35-mediated pathway and how cell surface calreticulin modulates this process. Although genetically determined Clq deficiency is a rare condition, it emphasizes the importance of Clq and its receptors. These studies of Clq receptor biology will provide insights into the pathogenesis of more common autoimmune diseases.

描述（由申请人提供）：Clq和MBL分别通过标记凋亡和坏死组织来参与组织重塑。 Clq 缺乏与 93% 的几率发生狼疮样综合征有关，其特征是早期出现严重皮疹和肾炎，发病率和死亡率很高。这种惊人的关联表明 Clq 在预防自身免疫方面发挥着重要作用，这必须依赖于与 Clq 受体的相互作用，因为 C4 和 C2 缺陷的表型要轻得多。我们的实验室已证明 Clq 和 MBL 与造血细胞上的补体受体 1 (CD35) 特异性结合。提出了两个假设将 Clq 缺陷与自身免疫联系起来。首先，B细胞上CD35的Clq依赖性连接可能引发抑制B细胞增殖的负信号。其次，细胞凋亡物质的Clq依赖性调理作用和CD35+吞噬细胞的清除可防止自身抗原变得具有免疫原性。该提案的三个目的是：(1)更精确地确定CD35上的Clq的结合位点和Clq上的CD35的结合位点。 (2)定义CD35的Clq连接对白细胞的功能影响，包括CD35对B细胞和吞噬细胞利用的相关信号传导途径。 (3)评估Clq调理的凋亡物质通过CD35介导的途径被摄取的能力以及细胞表面钙网蛋白如何调节该过程。尽管基因决定的 Clq 缺乏症是一种罕见疾病，但它强调了 Clq 及其受体的重要性。这些 Clq 受体生物学研究将为更常见的自身免疫性疾病的发病机制提供见解。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A role for lipid rafts in C1q-triggered O2- generation by human neutrophils.

DOI：
10.1016/j.molimm.2004.03.029
发表时间：
2004-06
期刊：
Molecular immunology
影响因子：
3.6
作者：
Iyore Otabor;S. Tyagi;F. Beurskens;I. Ghiran;P. Schwab;A. Nicholson‐Weller;L. Klickstein
通讯作者：
Iyore Otabor;S. Tyagi;F. Beurskens;I. Ghiran;P. Schwab;A. Nicholson‐Weller;L. Klickstein

Complement receptor 1/CD35 is a receptor for mannan-binding lectin.

补体受体1/CD35是曼南结合凝集素的受体。