Abstract：
Neutrophils are critical for inflammation and innate immunity, and their adhesion to vascular endothelium is a crucial step in neutrophil recruitment. Mitofusin-2 (MFN2) is required for neutrophil adhesion, but molecular details are unclear. Here, we demonstrated that β2 -integrin-mediated slow-rolling and arrest, but not PSGL-1-mediated cell rolling, are defective in MFN2-deficient neutrophil-like HL60 cells. This adhesion defect is associated with reduced expression of fMLP (N-formylmethionyl-leucyl-phenylalanine) receptor FPR1 as well as the inhibited β2 integrin activation, as assessed by conformation-specific monoclonal antibodies. MFN2 deficiency also leads to decreased actin polymerization, which is important for β2 integrin activation. Mn2+ -induced cell spreading is also inhibited after MFN2 knockdown. MFN2 deficiency limited the maturation of β2 integrin activation during the neutrophil-directed differentiation of HL60 cells, which is indicated by CD35 and CD87 markers. MFN2 knockdown in β2-integrin activation-matured cells (CD87high population) also inhibits integrin activation, indicating that MFN2 directly affects β2 integrin activation. Our study illustrates the function of MFN2 in leukocyte adhesion and may provide new insights into the development and treatment of MFN2 deficiency-related diseases.
摘要：
中性粒细胞对炎症和先天免疫至关重要，它们与血管内皮的粘附是中性粒细胞募集的关键步骤。中性粒细胞粘附需要Mitofusin-2（MFN2），但分子细节尚不清楚.这里,我们证明了β2-整合素介导的缓慢滚动和停滞，但不是PSGL-1介导的细胞滚动，在MFN2缺陷的嗜中性粒细胞样HL60细胞中存在缺陷。这种粘附缺陷与fMLP（N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸）受体FPR1的表达降低以及β2整合素激活抑制有关，通过构象特异性单克隆抗体评估。MFN2缺乏也导致肌动蛋白聚合降低，这对于β2整合素激活是重要的。Mn2+诱导的细胞铺展在MFN2敲低后也被抑制。MFN2缺乏限制了HL60细胞中性粒细胞定向分化过程中β2整合素激活的成熟，其由CD35和CD87标志物指示。在β2-整合素激活成熟细胞（CD87high群体）中的MFN2敲低也抑制整合素激活，表明MFN2直接影响β2整合素的活化。我们的研究说明了MFN2在白细胞粘附中的功能，并可能为MFN2缺乏症相关疾病的发展和治疗提供新的见解。
