Human monocytes store and secrete preformed CCL5, independent of de novo protein synthesis,Journal of Leukocyte Biology

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Human monocytes store and secrete preformed CCL5, independent of de novo protein synthesis
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2021-06-11 , DOI: 10.1002/jlb.3a0820-522rr
Arvin Tejnarine Persaud ₁ , Stephen Andrew Bennett ₁ , Laxshaginee Thaya _{1,

2} , Jonathan Burnie _{1,

2} , Christina Guzzo _{1,

2}

Affiliation

Monocytes are a subset of circulating peripheral blood mononuclear cells with diverse roles in immunity, including sentinel roles in cytokine secretion. Conventionally, cytokines require an inductive stimulus for their expression and secretion, resulting in a time lag from the time of stimulation to when the proteins are packaged and secreted. Because cytokines are the main communicators in the immune system, their temporal expression is a key factor in coordinating responses to efficiently resolve infection. Herein, we identify that circulating human monocytes contain preformed cytokines that are stored intracellularly, in both resting and activated states. Having preformed cytokines bypasses the time lag associated with de novo synthesis, allowing monocytes to secrete immune mediators immediately upon activation or sensing of microbe-associated molecular patterns. We demonstrate here that, out of several cytokines evaluated, human monocytes contain a previously undescribed reservoir of the preformed chemokine CCL5. Furthermore, we showed that CCL5 could be secreted from monocytes treated with the protein synthesis inhibitor (cycloheximide) and Golgi blocker (brefeldin A). We examined the possibility for uptake of extracellular CCL5 from platelet aggregates and observed no significant levels of platelet binding to our enriched monocyte preparations, indicating that the source of preformed CCL5 was not from platelets. Preformed CCL5 was observed to be distributed throughout the cytoplasm and partially colocalized with CD63+ and Rab11A+ membranes, implicating endosomal compartments in the intracellular storage and trafficking of CCL5.

中文翻译：

人类单核细胞储存和分泌预先形成的 CCL5，独立于从头蛋白质合成

单核细胞是循环外周血单核细胞的一个子集，在免疫中具有多种作用，包括在细胞因子分泌中的哨兵作用。通常，细胞因子的表达和分泌需要诱导性刺激，导致从刺激时间到蛋白质被包装和分泌的时间滞后。由于细胞因子是免疫系统中的主要传播者，它们的时间表达是协调反应以有效解决感染的关键因素。在这里，我们发现循环的人类单核细胞含有预先形成的细胞因子，这些细胞因子在静止和激活状态下都储存在细胞内。具有预先形成的细胞因子绕过了与从头合成相关的时间滞后，允许单核细胞在激活或感知微生物相关分子模式后立即分泌免疫介质。我们在此证明，在评估的几种细胞因子中，人类单核细胞含有先前未描述的预形成趋化因子 CCL5 的储库。此外，我们发现 CCL5 可以从用蛋白质合成抑制剂（放线菌酮）和高尔基体阻滞剂（布雷非菌素 A）处理的单核细胞中分泌。我们检查了从血小板聚集体中摄取细胞外 CCL5 的可能性，并没有观察到血小板与我们的富集单核细胞制剂结合的显着水平，这表明预制 CCL5 的来源不是来自血小板。观察到预制的 CCL5 分布在整个细胞质中，并与 CD63+ 和 Rab11A+ 膜部分共定位，

更新日期：2021-06-11

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