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Leukocyte Tetraspanin CD53 Restrains α3 Integrin Mobilization and Facilitates Cytoskeletal Remodeling and Transmigration in Mice
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-12 , DOI: 10.4049/jimmunol.1901054
Louisa Yeung 1, 2 , Jeremy M L Anderson 1 , Janet L Wee 1, 2 , Maria C Demaria 2 , Michaela Finsterbusch 1 , Yuxin S Liu 1 , Pam Hall 1 , Brodie C Smith 1 , Wendy Dankers 1 , Kirstin D Elgass 3 , Ian P Wicks 4, 5, 6 , Hang Fai Kwok 7 , Mark D Wright 2 , Michael J Hickey 8
Affiliation  

Key Points Absence of tetraspanin CD53 restricts neutrophil transmigration. CD53-deficient neutrophils show alterations in α3 integrin expression and trafficking. Serum-transfer arthritis is delayed in CD53-deficient mice. The importance of tetraspanin proteins in regulating migration has been demonstrated in many diverse cellular systems. However, the function of the leukocyte-restricted tetraspanin CD53 remains obscure. We therefore hypothesized that CD53 plays a role in regulating leukocyte recruitment and tested this hypothesis by examining responses of CD53-deficient mice to a range of inflammatory stimuli. Deletion of CD53 significantly reduced neutrophil recruitment to the acutely inflamed peritoneal cavity. Intravital microscopy revealed that in response to several inflammatory and chemotactic stimuli, absence of CD53 had only minor effects on leukocyte rolling and adhesion in postcapillary venules. In contrast, Cd53−/− mice showed a defect in leukocyte transmigration induced by TNF, CXCL1 and CCL2, and a reduced capacity for leukocyte retention on the endothelial surface under shear flow. Comparison of adhesion molecule expression in wild-type and Cd53−/− neutrophils revealed no alteration in expression of β2 integrins, whereas L-selectin was almost completely absent from Cd53−/− neutrophils. In addition, Cd53−/− neutrophils showed defects in activation-induced cytoskeletal remodeling and translocation to the cell periphery, responses necessary for efficient transendothelial migration, as well as increased α3 integrin expression. These alterations were associated with effects on inflammation, so that in Cd53−/− mice, the onset of neutrophil-dependent serum-induced arthritis was delayed. Together, these findings demonstrate a role for tetraspanin CD53 in promotion of neutrophil transendothelial migration and inflammation, associated with CD53-mediated regulation of L-selectin expression, attachment to the endothelial surface, integrin expression and trafficking, and cytoskeletal function.

中文翻译:

白细胞四跨膜蛋白 CD53 抑制 α3 整合素动员并促进小鼠的细胞骨架重塑和轮回

关键点 缺乏四跨膜蛋白 CD53 会限制中性粒细胞迁移。CD53 缺陷的中性粒细胞显示 α3 整合素表达和运输的改变。CD53 缺陷小鼠的血清转移性关节炎延迟。已经在许多不同的细胞系统中证明了四跨膜蛋白在调节迁移中的重要性。然而,白细胞限制性四跨膜蛋白 CD53 的功能仍然不清楚。因此,我们假设 CD53 在调节白细胞募集中起作用,并通过检查 CD53 缺陷小鼠对一系列炎症刺激的反应来检验这一假设。CD53 的缺失显着减少了急性发炎腹腔的中性粒细胞募集。活体显微镜显示,响应于几种炎症和趋化刺激,CD53 的缺失对毛细血管后小静脉中的白细胞滚动和粘附只有很小的影响。相比之下,Cd53-/- 小鼠显示出由 TNF、CXCL1 和 CCL2 诱导的白细胞迁移缺陷,以及在剪切流下白细胞在内皮表面保留的能力降低。野生型和 Cd53-/- 中性粒细胞中粘附分子表达的比较显示 β2 整联蛋白的表达没有改变,而 Cd53-/- 中性粒细胞中几乎完全不存在 L-选择蛋白。此外,Cd53-/- 中性粒细胞显示出激活诱导的细胞骨架重塑和向细胞外周易位、有效跨内皮迁移所需的反应以及α3 整合素表达增加方面的缺陷。这些改变与对炎症的影响有关,因此在 Cd53-/- 小鼠中,嗜中性粒细胞依赖性血清诱导关节炎的发作被推迟。总之,这些发现证明了四跨膜蛋白 CD53 在促进中性粒细胞跨内皮迁移和炎症中的作用,这与 CD53 介导的 L-选择素表达调节、与内皮表面的附着、整合素表达和运输以及细胞骨架功能有关。
更新日期:2020-06-12
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