Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and Migration
Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and Migration
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DOI：
10.1155/2020/2713074
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发表时间：
2020-04-07
影响因子：
4.6
通讯作者：
Bourgoin，Sylvain G.
中科院分区：
文献类型：
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作者：
Gamara，Jouda;Davis，Lynn;Bourgoin，Sylvain G.
趋化剂感知、粘附和迁移是中性粒细胞（pmn）向炎症或感染部位募集的关键事件。白细胞粘附或迁移缺陷导致以复发性感染为特征的免疫缺陷疾病。在这项研究中，我们利用PMN - Arf6条件敲除（cKO）小鼠，评估了Arf6对PMN体外粘附和向炎症部位迁移的作用。在PMN - like PLB - 985中，Arf6 fMLP介导的β2整合素配体、ICAM - 1和纤维蛋白原或β1/β2整合素配体纤维连接蛋白的粘附性显著降低。此外，野生型Arf6的过表达促进了基础和fMLP诱导的对固定整合素配体的粘附，而显性阴性Arf6的过表达则具有相反的作用。使用elane - credeletion小鼠菌株，我们报告了与从骨髓分离的naïve细胞相比，从背气袋分离的炎性PMNs中Arf6的缺失水平更强。在PMN‐Arf6 cKO小鼠中，注射LPS或化学引诱剂fMLP后，PMN向背气袋的募集明显减少。在Arf6 cKO PMNs中，细胞迁移受损与细胞表面CD11a和CD11b表达降低相关。我们的研究结果强调，Arf6调节PMN整合素的活性和可能的再循环，这阻碍了PMN向炎症部位的迁移。
Chemoattractant sensing, adhesiveness, and migration are critical events underlying the recruitment of neutrophils (PMNs) to sites of inflammation or infection. Defects in leukocyte adhesion or migration result in immunodeficiency disorders characterized by recurrent infections. In this study, we evaluated the role of Arf6 on PMN adhesionin vitroand on migration to inflammatory sites using PMN‐Arf6 conditional knockout (cKO) mice. In PMN‐like PLB‐985 silenced for Arf6 fMLP‐mediated adhesion to theβ2 integrin ligands, ICAM‐1 and fibrinogen or theβ1/β2 integrin ligand fibronectin was significantly reduced. Furthermore, overexpression of wild‐type Arf6 promoted basal and fMLP‐induced adhesion to immobilized integrin ligands, while overexpression of the dominant‐negative Arf6 has the opposite effects. Using theElane-Credeleting mouse strains, we report that the level of Arf6 deletion in inflammatory PMNs isolated from the dorsal air pouches was stronger when compared to naïve cells isolated from the bone marrow. In PMN‐Arf6 cKO mice, the recruitment of PMNs into the dorsal air pouch injected with LPS or the chemoattractant fMLP was significantly diminished. Impaired cell migration correlated with reduced cell surface expression of CD11a and CD11b in Arf6 cKO PMNs. Our results highlight that Arf6 regulates the activity and possibly the recycling of PMN integrins, and this compromises PMN migration to inflammatory sites.