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）：肥大细胞是各种炎症性疾病状态中的重要效应子。尽管组织肥大细胞的数量增加是哮喘，关节炎和纤维化疾病的一致特征，但对加速肥大细胞生长或维持其生存的机制鲜为人知，超出了干细胞因子（SCF）及其受体C-KIT的本构态输入。我们的初步表征了人类肥大细胞的有效生长因子，该生长因子由人类肥大细胞系自发分泌。它在功能上与SCF不同，并且使原代人肥大细胞具有抗传统C-KIT抑制剂的抗性。该提案的目的是隔离和纯化因子，确定其氨基酸序列，并开发出确定其表达部位的探针和抗体，以确定其大型支气管活检中的大量支气管生物群体与严重哮喘的人类受试者的关系。鉴于肥大细胞的重要性以及关于控制人类发展的机制的知识有限，这些研究具有直接的转化和治疗意义。