The Janus-like role of neuraminidase isoenzymes in inflammation.
The Janus-like role of neuraminidase isoenzymes in inflammation.
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DOI：
10.1096/fj.202101218r
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发表时间：
2022-05
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免疫细胞的激活、外渗和迁移到一个部位的过程是诱导急性炎症反应的早期和必要的步骤。这些事件是涉及多个监管步骤的煽动性级联的重要组成部分。利用以脂多糖为炎症诱导剂的小鼠气囊炎症模型，我们证明了神经氨酸酶家族的同工酶(NEU1、3和4)在这些过程中起着重要的作用，它是白细胞渗透的正负调节因子。对不同neu基因敲除(KO)小鼠(Neu1、Neu3、Neu3、Neu4、Neu3/4双KO小鼠)内毒素气囊炎模型进行炎症部位白细胞计数和免疫组织化学分析。我们的数据显示，在NEU1和NEU3缺乏的小鼠中，白细胞募集减少，而在NEU4缺乏的动物中，白细胞募集增加。与这些结果一致的是，Neu1小鼠全身和眼袋渗出液中的促炎细胞因子水平降低，而Neu4和KO小鼠的促炎细胞因子水平增加。针对NEU1、NEU3和NEU4亚型的药理抑制剂也会影响白细胞的募集。总之，我们的数据表明，neu同工酶对白细胞募集有明显的-甚至相反的-影响，因此值得进一步研究，以确定它们作为炎症级联反应调节因子的机制和重要性。
The processes of activation, extravasation, and migration of immune cells to a site are early and essential steps in the induction of an acute inflammatory response. These events are an essential part of the inflammatory cascade, which involves multiple regulatory steps. Using a murine air pouch model of inflammation with LPS as an inflammation inducer, we demonstrate that isoenzymes of the neuraminidase family (NEU1, 3, and 4) play essential roles in these processes by acting as positive or negative regulators of leukocyte infiltration. In genetically knocked‐out (KO) mice for different NEU genes (Neu1 KO, Neu3 KO, Neu4 KO, and Neu3/4 double KO mice) with LPS‐induced air pouch inflammation, leukocytes at the site of inflammation were counted, and the inflamed tissue was analyzed using immunohistochemistry. Our data show that leukocyte recruitment was decreased in NEU1‐ and NEU3‐deficient mice, while it was increased in NEU4‐deficient animals. Consistent with these results, systemic as well as pouch exudate levels of pro‐inflammatory cytokines were reduced in Neu1 and increased in Neu4 KO mice. Pharmacological inhibitors specific for NEU1, NEU3, and NEU4 isoforms also affected leukocyte recruitment. Together our data demonstrate that NEU isoenzymes have distinct—and even opposing—effects on leukocyte recruitment, and therefore warrant further investigation to determine their mechanisms and importance as regulators of the inflammatory cascade.