In Utero Sensitization to Allergens & Pollution

基于实验室的呼吸机制研究项目机制研究项目：子宫内对过敏原的敏化和环境污染物的作用。最近的证据表明抗原致敏，定义为抗原诱导的脐带血单个核细胞（CPMC）增殖试验，发生在产前。例如，我们的工作表明，抗原诱导的CBMC增殖发生在体外刺激与多种吸入室内过敏原普遍存在于城市，包括蟑螂和老鼠。其他实验研究表明，柴油尾气颗粒物（DEP），特别是DEP中的多环芳烃（PAH）成分，可以增强抗原特异性致敏性和抗氧化性

The Laboratory-Based Respiratory Mechanistic Research Project Mechanistic Research Project: In Utero Sensitization to Allergens and the Role of Environmental Pollutants. Recent evidence suggests that antigen sensitization, defined as antigen-induced cord blood mononuclear cell (CPMC) proliferation assays, occurs prenatally. For example, our work demonstrates that antigen-induced CBMC proliferation occurs following in vitro stimulation with multiple inhaled indoor allergens prevalent in inner-cities, including cockroach and mouse. Other experimental research has indicated that diesel exhaust particulates (DEP), and particularly the polycyclic aromatic hydrocarbon (PAH) component of DEP, can augment antigen-specific sensitization and IgE-mediated processes. The occurrence of antigen-specific immune responses in utero may have important implications for the subsequent onset of respiratory disease, particularly in light of the high prevalence of both environmental indoor allergens and DEP in northern Manhattan and elsewhere, and their apparent role in asthma. Yet the effect of prenatal sensitization on subsequent airway hyperreactivity and antigen-induced inflammation characteristic of asthma is not understood. In addition, the importance of environmental pollutants (egs DEP, endotoxin) to the onset of prenatal antigen-specific sensitization also has not been elucidated. The project will test the hypotheses that in utero sensitization increases the risk for subsequent airway hyperreactivity and antigen-induced inflammation, and that environmental exposure to DEP promotes antigen-specific sensitization in utero, whereas exposure to endotoxin is protective. The goal is to use mouse models to determine the importance of in utero sensitization to subsequent airway hyperreactivity and inflammation, and to determine whether the mechanism of in utero sensitization involves the interaction of multiple urban environmental exposures. Ultimately, these studies could lead to a better understanding of asthma pathogenesis, and ultimately better strategies for asthma prevention. Specifically, the aims are to: Aim 1. Determine whether in utero sensitization increases the risk for subsequent airway hyperreactivity and antigen-induced inflammation. Aim 2. Determine whether DEP, endemic to the northern Manhattan environment, promote antigen-specific prenatal sensitization, and whether this occurs by upregulating Th2-mediated allergic responses. We will also determine whether PAH, measured by PAH-adducts in lung tissue, mediates this response. Aim 3. Determine whether endotoxin protects from the development of antigen-specific prenatal sensitization, and whether this occurs by upregulating Th1-mediated immune processes.