权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Characterization of a Novel Growth and Survival Factor for Human Mast Cells

人类肥大细胞新型生长和生存因子的表征

基本信息

批准号：
8977481
负责人：
Joshua A Boyce
金额：
$ 26.63万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-12-05 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8977481
关键词：
A/J Mouse Amino Acid Sequence Antibodies Apoptosis Arthritis Asthma Biopsy Breathing CD34 gene Cell Count Cell Culture Techniques Cell Line Cells Cellular biology Chemicals Collectins Culture Media Detection Development Differentiation and Growth Digestion Disease Drug Targeting Effector Cell Eicosanoids Extrinsic asthma Glucocorticoids Goals Growth Health Heating Helminths Hematopoietic Histamine Human Hypersensitivity Imatinib In Vitro Inflammation Mediators Inflammatory Interleukin-3 Interleukin-4 Interleukin-5 Interleukin-6 Interleukin-9 Intestinal Mucosa Knowledge Lead Ligands Longevity Malignant Neoplasms Mediator of activation protein Mus Natural Immunity Pathogenesis Patients Peptide Hydrolases Physiological Proliferating Protein Tyrosine Kinase Proteins Proto-Oncogene Protein c-kit Recombinants Resistance Rheumatoid Arthritis Role Sentinel Signal Pathway Site Skin Source Stem Cell Factor Stem cells Therapeutic Tissues Tyrosine Kinase Inhibitor Umbilical Cord Blood aspirin-exacerbated respiratory disease cytokine human disease human subject improved in vivo inhibitor/antagonist lipid mediator mast cell mastocytosis molecular diagnostics novel receptor

项目摘要

DESCRIPTION (provided by applicant): Mast cells are important effectors in a wide array of inflammatory disease states. Although increases in the numbers of tissue mast cells are a consistent feature of asthma, arthritis, and fibrotic diseases, there is little known about the mechanisms that accelerate mast cell growth or sustain their survival beyond the constitutive input from stem cell factor (SCF) and its receptor, c-kit. We have preliminarily characterized a potent growth factor for human mast cells that is secreted spontaneously by a human mast cell line. It is functionally distinct from SCF, and renders primary human mast cells resistant to conventional c-kit inhibitors. The goal of this proposal is to isolate and purify the factor, determine its amino acid sequence, and develop the probes and antibodies needed to determine its sites of expression and its relationship to mast cell hyperplasia in a large collectin of bronchial biopsies from human subjects with severe asthma. Given the importance of mast cells and the limited body of knowledge regarding the mechanisms that control their development in humans, these studies have direct translational and therapeutic implications.

描述（由申请人提供）：肥大细胞是多种炎症疾病状态中的重要效应器。尽管组织肥大细胞数量的增加是哮喘、关节炎和纤维化疾病的一致特征，但除了干细胞因子 (SCF) 及其受体 c-kit 的组成性输入之外，加速肥大细胞生长或维持其生存的机制却知之甚少。我们初步鉴定了人类肥大细胞系自发分泌的一种有效的人类肥大细胞生长因子。它在功能上与 SCF 不同，并且使原代人类肥大细胞对传统的 c-kit 抑制剂具有抗性。该提案的目标是分离和纯化该因子，确定其氨基酸序列，并开发所需的探针和抗体，以确定其表达位点及其与严重哮喘人类受试者支气管活检中肥大细胞增生的关系。鉴于肥大细胞的重要性以及关于控制其在人类发育的机制的知识体系有限，这些研究具有直接的转化和治疗意义。