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Zhichao Fan, Wei Liu, Yueyang Wang, Alan Y Hsu, Tao Lin, Hao Sun, Joel S Pachter, Alex Groisman, Matthew Imperioli, Fernanda Wajnsztajn Yungher, Liang Hu, Penghua Wang, Qing Deng, Mitofusin-2 regulates leukocyte adhesion through the maturation of beta2 integrin activation in differentiation, The Journal of Immunology, Volume 206, Issue 1_Supplement, May 2021, Page 11.01, https://doi.org/10.4049/jimmunol.206.Supp.11.01
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Abstract
Neutrophils are critical in inflammation and innate immunity. Neutrophil adhesion to vascular endothelium is a crucial step in neutrophil recruitment. Mitofusin-2 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 mitofusin-2-deficient neutrophil-like HL60 cells. This adhesion defect is associated with reduced expression of fMLP receptors and β2 integrins as well as the inhibited β2 integrin activation, as assessed by conformational-specific antibodies. Mitofusin-2 deficiency limited the maturation of β2 integrin activation during the neutrophil-directed differentiation of HL60 cells, which is indicated by identified markers CD35 and CD87. Reversed to results in overall HL60 cells, mitofusin-2 knockdown in β2-integrin-activation-matured cells (CD87high population) enhanced integrin activation. Our study illustrates the function of mitofusin-2 in leukocyte adhesion and may provide new insights into the development and treatment of mitofusin-2-deficiency-related disease.