ABSTRACT

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 in vitro, treated with DHA, and exposed to a multi-walled carbon nanotube (MWNCT) or crystalline silica (SiO₂). 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 in vivo, 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 in vitro findings, DHA increased pulmonary inflammation and LMP. These results suggest that pulmonary responses in vivo may not necessarily be predicted from single-cell responses in vitro.

摘要

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 omega-3 多不饱和脂肪酸，显示出抗炎能力。DHA 对颗粒引起的炎症的影响尚不清楚；因此，本研究的目的是检验 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的假设。分离的 Balb/c 肺泡巨噬细胞 (AM)在体外被极化为 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 ₂）。结果显示细胞毒性最小、对二氧化硅颗粒吸收的强大影响以及表型之间的 LMP 差异。二十二碳六烯酸在 M2c 表型中最大程度地阻止了这些影响。为了确定 DHA在体内是否同样影响炎症，将 Balb/c 小鼠置于对照或 1% DHA 饮食 3 周，滴入相同的颗粒，并在滴注后 24 小时进行评估。数据表明，与体外研究结果相比，DHA 增加了肺部炎症和 LMP。这些结果表明，体内的肺反应不一定可以从体外的单细胞反应中预测出来。