Route of administration significantly affects particle deposition and cellular recruitment.

Route of administration significantly affects particle deposition and cellular recruitment.
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DOI:
10.1371/journal.pone.0289373
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发表时间:
2023
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
文献类型:
--
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肺暴露于粉尘、污染物和其他气溶胶微粒已知与肺部疾病如哮喘和慢性阻塞性肺病相关。这些健康影响归因于气溶胶组分诱导肺部炎症的能力,其促进组织重塑,包括纤维化、组织降解和平滑肌增殖。因此,这些效应的分布可对肺的生理功能产生显著影响。为了研究吸入颗粒物的分布对肺部发病的影响,我们比较了不同的颗粒物输送方法的效果。通过比较荧光微球的鼻内递送与气雾剂递送,我们观察到明显不同的颗粒沉积模式;鼻内递送提供集中在较大气道上的集中沉积,而气雾剂递送在整个肺实质中显示不成形的沉积。认识到炎症细胞的影响取决于它们的募集和行为,我们假设这些分布模式的变化可能导致生物反应的显著改变。为了阐明这些发现在生物学表征方面的相关性,我们随后在转基因中性粒细胞报告小鼠模型中对内毒素(细菌脂多糖或LPS)给药引起的反应进行了研究。与微球结果一样,招募的中性粒细胞炎症反应模式与递送方法相匹配;也就是说,尽管中性粒细胞具有主动迁移行为,但炎症组织病理学模式要么集中在大气道(鼻内给药),要么弥漫在整个实质(气雾剂)。这些结果证明了气雾剂递送模式的重要性,因为不同的炎症和组织重塑模式将对肺生理学产生不同的影响。
Lung exposures to dusts, pollutants, and other aerosol particulates are known to be associated with pulmonary diseases such as asthma and Chronic Obstructive Pulmonary Disease. These health impacts are attributed to the ability of aerosol components to induce pulmonary inflammation, which promotes tissue remodeling, including fibrosis, tissue degradation, and smooth muscle proliferation. Consequently, the distribution of these effects can have a significant impact on the physiologic function of the lung. In order to study the impact of distribution of inhaled particulates on lung pathogenesis, we compared the effect of different methods of particle delivery. By comparing intranasal versus aerosol delivery of fluorescent microspheres, we observed strikingly distinct patterns of particle deposition; intranasal delivery provided focused deposition concentrated on larger airways, while aerosol delivery showed unform deposition throughout the lung parenchyma. Recognizing that the impacts of inflammatory cells are contingent upon their recruitment and behavior, we postulate that these variations in distribution patterns can result in significant alterations in biological responses. To elucidate the relevance of these findings in terms of biological representation, we subsequently conducted an investigation into the responses elicited by the administration of endotoxin (bacterial Lipopolysaccharide, or LPS) in a transgenic neutrophil reporter mouse model. As with the microsphere results, patterns of recruited neutrophil inflammatory responses matched the delivery method; that is, despite the active migratory behavior of neutrophils, inflammatory histopathology patterns were either focused on large airways (intranasal administration) or diffusely throughout the parenchyma (aerosol). These results demonstrate the importance of modes of aerosol delivery as different patterns of inflammation and tissue remodeling will have distinct impacts on lung physiology.
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DOI: 10.1063/1.5042097
发表时间: 2019-03-01
影响因子: 1.6
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DOI: 10.1089/jam.2006.19.110
发表时间: 2006-03-01
期刊: JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG
影响因子: --
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