Pulmonary sarcoidosis has unknown etiology, a difficult diagnostic procedure and no curative treatment. Extracellular vesicles including exosomes are nano-sized entities released from all cell types. Previous studies of exosomes from bronchoalveolar lavage fluid (BALF) of sarcoidosis patients have revealed pro-inflammatory components and abilities, but cell sources and mechanisms have not been identified. In the current study, we found that BALF exosomes from sarcoidosis patients, but not from healthy individuals, induced a dose-dependent elevation of intracellular IL-1β in monocytes. Analyses of supernatants showed that patient exosomes also induced release of IL-1β, IL-6 and TNF from both PBMCs and enriched monocytes, suggesting that the observed effect is direct on monocytes. The potently chemotactic chemokine CCL2 was induced by exosomes from a subgroup of patients, and in a blocking assay the exosome-induced CCL2 was reduced for 13 out of 19 patients by the asthma drug Montelukast, a cysteinyl leukotriene receptor antagonist. Further, reactive oxygen species generation by PBMCs was induced to a higher degree by patient exosomes compared to healthy exosomes. These findings add to an emerging picture of exosomes as mediators and disseminators of inflammation, and open for further investigations of the link between CCL2 and exosomal leukotrienes in sarcoidosis.

肺结节病病因不明，诊断程序困难且无治疗方法。包括外泌体的细胞外囊泡是从所有细胞类型释放的纳米级实体。先前对结节病患者的支气管肺泡灌洗液（BALF）的外来体的研究显示了促炎成分和能力，但尚未确定细胞来源和机制。在当前研究中，我们发现结节病患者而非健康个体的BALF外泌体诱导了单核细胞中细胞内IL-1β的剂量依赖性升高。上清液的分析表明，患者外泌体还诱导了PBMC和富集的单核细胞释放IL-1β，IL-6和TNF，这表明观察到的作用直接作用于单核细胞。有效的趋化趋化因子CCL2是由亚组患者的外泌体诱导的，在阻断试验中，哮喘药物Montelukast（一种半胱氨酰白三烯受体拮抗剂）在19位患者中有13位减少了外泌体诱导的CCL2。此外，与健康外泌体相比，患者外泌体在更高程度上诱导了PBMCs产生的活性氧。这些发现增加了外来体作为炎症的传播者和传播者的画面，并为进一步研究结节病中CCL2与外体白三烯之间的联系打开了大门。与健康外泌体相比，患者外泌体在更大程度上诱导了PBMCs产生的活性氧。这些发现增加了外来体作为炎症的传播者和传播者的画面，并为进一步研究结节病中CCL2与外体白三烯之间的联系打开了大门。与健康外泌体相比，患者外泌体在更大程度上诱导了PBMCs产生的活性氧。这些发现增加了外来体作为炎症的传播者和传播者的画面，并为进一步研究结节病中CCL2与外体白三烯之间的联系打开了大门。