BACKGROUND Leukotriene B4 (LTB4) is a potent inflammatory mediator that also stimulates the immune response. In addition, it promotes polymorphonuclear leukocyte phagocytosis, chemotaxis, chemokinesis and modulates cytokines release. Regarding chemical instability of the leukotriene molecule, in the present study we assessed the immunomodulatory activities conferred by LTB4 released from microspheres (MS). A previous oil-in-water emulsion solvent extraction-evaporation method was chosen to prepare LTB4-loaded MS. RESULTS In the mice cremasteric microcirculation, intraescrotal injection of 0.1 ml of LTB4-loaded MS provoked significant increases in leukocyte rolling flux, adhesion and emigration besides significant decreases in the leukocyte rolling velocity. LTB4-loaded MS also increase peroxisome proliferator-activated receptor-alpha (PPARalpha) expression by murine peritoneal macrophages and stimulate them to generate nitrite levels. Monocyte chemoattractant protein-1 (MCP-1) and nitric oxide (NO) productions were also increased when human umbilical vein and artery endothelial cells (HUVECs and HUAECs, respectively) were stimulated with LTB4-loaded MS. CONCLUSION LTB4-loaded MS preserve the biological activity of the encapsulated mediator indicating their use as a new strategy to modulate cell activation, especially in the innate immune response.

中文翻译：

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载有白三烯 B4 的微球：一种调节细胞活化的新治疗策略。

背景白三烯B4 (LTB4) 是一种有效的炎症介质，它也能刺激免疫反应。此外，它还促进多形核白细胞的吞噬作用、趋化性、趋化作用并调节细胞因子的释放。关于白三烯分子的化学不稳定性，在本研究中，我们评估了微球 (MS) 释放的 LTB4 赋予的免疫调节活性。选择以前的水包油乳液溶剂萃取-蒸发方法来制备负载 LTB4 的 MS。结果 在小鼠提睾微循环中，阴囊内注射 0.1 ml 负载 LTB4 的 MS 除了显着降低白细胞滚动速度外，还引起白细胞滚动通量、粘附和迁移显着增加。加载 LTB4 的 MS 还通过小鼠腹腔巨噬细胞增加过氧化物酶体增殖物激活受体-α (PPARalpha) 的表达，并刺激它们产生亚硝酸盐水平。当人脐静脉和动脉内皮细胞（分别为 HUVEC 和 HUAEC）用负载 LTB4 的 MS 刺激时，单核细胞趋化蛋白-1 (MCP-1) 和一氧化氮 (NO) 的产生也会增加。结论 负载 LTB4 的 MS 保留了封装介质的生物活性，表明它们可用作调节细胞活化的新策略，尤其是在先天免疫反应中。当人脐静脉和动脉内皮细胞（分别为 HUVEC 和 HUAEC）用负载 LTB4 的 MS 刺激时，单核细胞趋化蛋白-1 (MCP-1) 和一氧化氮 (NO) 的产生也会增加。结论 负载 LTB4 的 MS 保留了封装介质的生物活性，表明它们可用作调节细胞活化的新策略，尤其是在先天免疫反应中。当人脐静脉和动脉内皮细胞（分别为 HUVEC 和 HUAEC）用负载 LTB4 的 MS 刺激时，单核细胞趋化蛋白-1 (MCP-1) 和一氧化氮 (NO) 的产生也会增加。结论 负载 LTB4 的 MS 保留了封装介质的生物活性，表明它们可用作调节细胞活化的新策略，尤其是在先天免疫反应中。