Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
IDEXX Laboratories Pty. Ltd., Rydalmere, New South Wales, Australia.
PLoS One. 2023 Mar 15;18(3):e0282738. doi: 10.1371/journal.pone.0282738. eCollection 2023.
Alveolar macrophages (AMs) are the predominant innate immune cell in the distal respiratory tract. During inflammatory responses, AMs may be supplemented by blood monocytes, which differentiate into monocyte-derived macrophages (MDMs). Macrophages play important roles in a variety of common equine lower airway diseases, including severe equine asthma (SEA). In an experimental model, an inhaled mixture of Aspergillus fumigatus spores, lipopolysaccharide, and silica microspheres (FLS), induced SEA exacerbation in susceptible horses. However, whether equine AMs and MDMs have differing immunophenotypes and cytokine responses to FLS stimulation is unknown. To address these questions, alveolar macrophages/monocytes (AMMs) were isolated from bronchoalveolar lavage fluid and MDMs derived from blood of six healthy horses. Separately, AMMs and MDMs were cultured with and without FLS for six hours after which cell surface marker expression and cytokine production were analyzed by flow cytometry and a bead-based multiplex assay, respectively. Results showed that regardless of exposure conditions, AMMs had significantly higher surface expression of CD163 and CD206 than MDMs. Incubation with FLS induced secretion of IL-1β, IL-8, TNF-α and IFN-γ in AMMs, and IL-8, IL-10 and TNF-α in MDMs. These results suggest that AMMs have a greater proinflammatory response to in vitro FLS stimulation than MDMs, inferring differing roles in equine lung inflammation. Variability in recruitment and function of monocyte-macrophage populations warrant more detailed in vivo investigation in both homeostatic and diseased states.
肺泡巨噬细胞(AMs)是远端呼吸道中主要的先天免疫细胞。在炎症反应中,AMs 可能会被血液单核细胞补充,后者分化为单核细胞衍生的巨噬细胞(MDMs)。巨噬细胞在多种常见的马下呼吸道疾病中发挥重要作用,包括严重马哮喘(SEA)。在一个实验模型中,吸入烟曲霉孢子、脂多糖和二氧化硅微球(FLS)混合物可使易感马的 SEA 恶化。然而,尚不清楚马 AM 和 MDM 对 FLS 刺激是否具有不同的免疫表型和细胞因子反应。为了解决这些问题,从支气管肺泡灌洗液中分离出肺泡巨噬细胞/单核细胞(AMMs),并从六匹健康马的血液中分离出 MDM。分别将 AMMs 和 MDM 与 FLS 一起培养和不培养 6 小时,然后通过流式细胞术和基于珠子的多重分析分别分析细胞表面标志物表达和细胞因子产生。结果表明,无论暴露条件如何,AMMs 的 CD163 和 CD206 表面表达均明显高于 MDM。用 FLS 孵育可诱导 AMMs 分泌 IL-1β、IL-8、TNF-α 和 IFN-γ,以及 MDM 分泌 IL-8、IL-10 和 TNF-α。这些结果表明,AMMs 对体外 FLS 刺激的促炎反应大于 MDM,推断在马肺部炎症中具有不同的作用。单核细胞-巨噬细胞群的募集和功能的可变性需要在稳态和疾病状态下对其进行更详细的体内研究。