Inflammation Program, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa, USA.
Department of Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, Michigan, USA.
J Leukoc Biol. 2021 Nov;110(5):917-925. doi: 10.1002/JLB.3AB0520-339RR. Epub 2021 Mar 8.
Neutrophils (PMN) regulate inflammation in many ways, including communication with other immune cells via extracellular vesicles (EVs). EVs released by human neutrophils activated with N-formylmethionyl-leucyl-phenylalanine (fMLF) (PMN-fMLF EVs) had an outside-out orientation and contained functionally important neutrophil plasma membrane proteins, including flavocytochrome b558, and enzymatically active granule proteins, elastase, and myeloperoxidase. Treatment of naïve PMN with PMN-fMLF EVs primed fMLF-stimulated NADPH oxidase activity, increased surface expression of the complement receptors CD11b/CD18 and CD35, the specific granule membrane protein CD66, and flavocytochrome b , and promoted phagocytosis of serum-opsonized Staphylococcus aureus. The primed oxidase activity reflected increased surface expression of flavocytochrome b558 and phosphorylation of SER345 in p47 , two recognized mechanisms for oxidase priming. Taken together, these data demonstrate that stimulated PMN released EVs that altered the phenotype of naïve phagocytes by priming of the NADPH oxidase activity and augmenting phagocytosis, two responses that are integral to optimal PMN host defense.
中性粒细胞 (PMN) 通过多种方式调节炎症，包括通过细胞外囊泡 (EV) 与其他免疫细胞进行通讯。用 N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸 (fMLF) 激活的人中性粒细胞释放的 EV (PMN-fMLF EV) 具有外向取向，并且包含功能上重要的中性粒细胞质膜蛋白，包括 flavocytochrome b558 和具有酶活性的颗粒蛋白，弹性蛋白酶和髓过氧化物酶。用 PMN-fMLF EV 处理幼稚 PMN 可引发 fMLF 刺激的 NADPH 氧化酶活性，增加补体受体 CD11b/CD18 和 CD35、特异性颗粒膜蛋白 CD66 和 flavocytochrome b 的表面表达，并促进血清调理的金黄色葡萄球菌的吞噬作用。被引发的氧化酶活性反映了 flavocytochrome b558 的表面表达增加和 p47 中 SER345 的磷酸化，这是氧化酶引发的两种公认机制。总之，这些数据表明，刺激的 PMN 释放的 EV 通过 NADPH 氧化酶活性的引发和吞噬作用的增强来改变幼稚吞噬细胞的表型，这两种反应是 PMN 宿主防御的重要组成部分。
