Sunday, November 24, 2024
11/24/2024
Project Summary/Abstract Ragweed is one of the most predominant aeroallergens in the world and is a major causative agent of allergic asthma in the global population. It is distributed widely; with increasing land growth and atmospheric aerosolization across continents while it maintains its integrity due to an outer shell that is one of the strongest biopolymers in nature. Air pollution, though, such as ground-level ozone, can induce significant and irreversible changes in ragweed pollen (RWP) structure and chemical composition. The effects of ozone-induced changes on RWP are poorly defined and represent an underappreciated consequence that ozone pollution may have on people with allergic asthma, leading to increased morbidity. The goal of this proposal is to define the effects of ozone on RWP and how these changes induce biological responses in vitro and in vivo that may exacerbate asthma immunopathologies. Using scanning electron microscopy (SEM), we have demonstrated that ozone exposure can lead to rupture of RWP grains, which may enhance release of sub pollen particles (SPPs) that easily enter the lower airways and promote inflammation. Using an in vivo model of asthma, we found ozone-exposed RWP (RWPO) induces mixed neutrophilic/eosinophils inflammation in the airways in addition to elevated type 2 cytokines and IL-6 levels in the lung as compared to unexposed RWP. When comparing defatted RWP (i.e, depleted of surface lipids) to untreated RWP, we found that airway inflammation is reduced in vivo and alveolar macrophage (AMs) and airway epithelial cells (AECs) produce less pro-inflammatory cytokines in vitro. Our central hypothesis is that environmental ozone induces changes in the chemical composition and structure of ragweed pollen grains, which result in increased activation of alveolar macrophages and lung epithelial cells and more advanced immunopathology of the airways. In Aim 1 we hypothesize that specific atmospheric conditions increase the effects of ozone exposure on the chemical composition of RWP and induce greater damage to pollen structure, allowing for easier fragmentation of pollen grains. In different UV light and humidity conditions, RWP will be exposed to ozone and then characterized for structure and morphology with SEM, surface molecular composition with Fourier transform infrared spectroscopy (FT-IR) and gas chromatography mass spectrometry (GC/MS), as well as forces required to break the pollen and to obtain SPPs. In Aim 2, we hypothesize that cell surface lipids from RWPO activate AMs and AECs and promote robust pulmonary inflammation in response to ragweed pollens. We will complete in vitro studies and in vivo mouse models of asthma with defatted and control RWPO to test this hypothesis. We bring together expertise in air pollution chemistry and allergic diseases to investigate the role of pollution directly on pollen grains and the mechanisms that promote pulmonary inflammation.
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