FcERI Expression, Cellular Sensitivity, In vivo Response

FcERI 表达、细胞敏感性、体内反应

• 批准号: 7150225
• 负责人: Donald W MacGlashan
• 金额: $ 24.62万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7150225
• 关键词: allergens; antibody receptor; antibody titering; antigen antibody reaction; basophils; biological signal transduction; cooperative study; histamine; human subject; immediate hypersensitivity; immunoglobulin E; laboratory mouse; mast cell; monoclonal antibody; pathologic process; patient oriented research; protein quantitation /detection; protein structure; protein structure function; receptor expression

Immediate hypersensitivity reactions result from the activation of mast cells at the interface between the outside environment and tissues such as airways, gastrointestinal tract and skin. IgE antibody binds to mast cells and basophils and upon aggregation of the receptor for IgE antibody, FceRI, the cell is activated to secrete a variety of mediators that cause the local and systemic response characteristic of allergies. It is well accepted that IgE mediates this kind of reaction but translation of this knowledge to the expression of allergic disease is poor. The question addressed in this project is how much IgE is necessary and what parameters adequately predict a response in an individual patient. Indirectly, this project asks whether these parameters alone are sufficient to account for responsiveness in vivo. The first aim directly addresses the issue and posits three critical parameters, IgE density on basophils or mast cells (which is itself regulated by IgE and other factors to be explored), the antigen-specific to total IgE ratio and the basophil (mast cell) sensitivity - a new parameter that is defined as the number of antigen-specific IgE molecules required for a 50% maximum response. A test of the importance of these three parameters is proposed which uses the drug omalizumab in cat allergic patients to manipulate IgE levels into each patients critical response region while measuring basophil and mast cell responses. The second aim focuses on the role of the beta subunit of FceRI on controlling basophil sensitivity to antigen stimulation and FceRI expression. This aim will also propose a manipulation of IgE levels in vivo to optimize changes induced by an experimental allergen challenge in vivo that is expected to alter cytokine levels that control FceRI beta expression. The primary goal is to assess the quantitative rates of receptor expression in vivo. The final two aims are related to aims 1 and 2; they examine the changes in signaling molecule expression during modulation of IgE in vivo and assess the rate of FceRI a synthesis in vivo using a unique method of analysis based on omalizumab-induced decay of FceRI expression.

直接的超敏反应是由细胞界面的肥大细胞激活引起的