Department of Biomedical and Pharmaceutical Sciences, Center for Environmental Health Sciences, University of Montana , Missoula, MT, USA.
Department of Food Science and Human Nutrition, Institute for Integrative Toxicology, Michigan State University , East Lansing, MI, USA.
J Toxicol Environ Health A. 2021 Feb 16;84(4):152-172. doi: 10.1080/15287394.2020.1842826. Epub 2020 Nov 4.
Inhalation of particles results in pulmonary inflammation; however, treatments are currently lacking. Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid shown to exhibit anti-inflammatory capabilities. The impact of DHA on particle-induced inflammation is unclear; therefore, the aim of this study was to examine the hypothesis that DHA downregulates macrophage inflammatory responses by altering phagolysosomal membrane permeability (LMP) and shifting macrophage phenotype. Isolated Balb/c alveolar macrophages (AM) were polarized into M1, M2a, M2b, or M2c phenotypes , treated with DHA, and exposed to a multi-walled carbon nanotube (MWNCT) or crystalline silica (SiO). Results showed minimal cytotoxicity, robust effects for silica particle uptake, and LMP differences between phenotypes. Docosahexaenoic acid prevented these effects to the greatest extent in M2c phenotype. To determine if DHA affected inflammation similarly , Balb/c mice were placed on a control or 1% DHA diet for 3 weeks, instilled with the same particles, and assessed 24 hr following instillation. Data demonstrated that in contrast to findings, DHA increased pulmonary inflammation and LMP. These results suggest that pulmonary responses may not necessarily be predicted from single-cell responses .
吸入颗粒会导致肺部炎症；然而，目前缺乏治疗方法。二十二碳六烯酸（DHA）是一种ω-3 多不饱和脂肪酸，具有抗炎作用。DHA 对颗粒诱导的炎症的影响尚不清楚；因此，本研究旨在检验以下假设：DHA 通过改变吞噬溶酶体膜通透性（LMP）和改变巨噬细胞表型来下调巨噬细胞炎症反应。分离的 Balb/c 肺泡巨噬细胞（AM）被极化到 M1、M2a、M2b 或 M2c 表型，用 DHA 处理，并暴露于多壁碳纳米管（MWNCT）或结晶二氧化硅（SiO）中。结果显示，细胞毒性最小，SiO 颗粒摄取具有强大的作用，表型之间的 LMP 存在差异。DHA 在 M2c 表型中最大程度地预防了这些作用。为了确定 DHA 是否对炎症有类似的影响，将 Balb/c 小鼠置于对照或 1%DHA 饮食中 3 周，用相同的颗粒注入，并在注入后 24 小时进行评估。数据表明，与研究结果相反，DHA 增加了肺部炎症和 LMP。这些结果表明，肺部反应可能不一定可以从单细胞反应中预测。
