In Utero Sensitization to Allergens & Pollution

机械研究项目：在过敏原过敏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核细胞（CPMC）增殖试验，发生产前。例如，我们的工作表明，抗原诱导的CBMC增殖发生后，在体外刺激多种吸入室内过敏原流行的城市，包括蟑螂和小鼠。其他实验研究已经表明，柴油机排气颗粒（DEP），特别是DEP的多环芳烃（PAH）组分，可以增加抗原特异性致敏作用， IgE介导的过程。子宫内抗原特异性免疫反应的发生可能对随后呼吸道疾病的发生具有重要意义，特别是鉴于北方曼哈顿和其他地方的环境室内过敏原和DEP的高患病率，以及它们在哮喘中的明显作用。然而，产前致敏对随后的气道高反应性和抗原诱导的哮喘炎症特征的影响尚不清楚。此外，环境污染物（如DEP、内毒素）对产前抗原特异性致敏的重要性也尚未阐明。该项目将测试以下假设：子宫内致敏增加随后气道高反应性和抗原诱导的炎症的风险，环境暴露于DEP促进子宫内抗原特异性致敏，而暴露于内毒素具有保护作用。我们的目标是使用小鼠模型，以确定子宫内致敏的重要性，随后的气道高反应性和炎症，并确定子宫内致敏的机制是否涉及多种城市环境暴露的相互作用。最终，这些研究可以更好地了解哮喘发病机制，并最终更好地预防哮喘。具体而言，目标是： 目标1.确定子宫内致敏是否会增加随后气道高反应性和抗原诱导炎症的风险。 目标2.确定是否DEP，地方性北方曼哈顿环境，促进抗原特异性产前致敏，以及是否通过上调Th2介导的过敏反应发生。我们还将确定肺组织中PAH加合物是否介导这种反应。 目标3。确定内毒素是否保护抗原特异性产前致敏的发展，以及是否通过上调Th1介导的免疫过程发生。

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.