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Mitofusin-2 (MFN2) is required for neutrophil adhesion, but molecular details are unclear. Here, we demonstrated that \u03b22-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 \u03b22 integrin activation, as assessed by conformation-specific monoclonal antibodies. MFN2 deficiency also leads to decreased actin polymerization, which is important for \u03b22 integrin activation. Mn2+-induced cell spreading is also inhibited after MFN2 knockdown. MFN2 deficiency limited the maturation of \u03b22 integrin activation during the neutrophil-directed differentiation of HL60 cells, which is indicated by CD35 and CD87 markers. MFN2 knockdown in \u03b22-integrin activation-matured cells (CD87high population) also inhibits integrin activation, indicating that MFN2 directly affects \u03b22 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.<\/jats:p>","DOI":"10.1002\/jlb.1a0720-471r","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T08:21:02Z","timestamp":1631089262000},"page":"771-791","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mitofusin-2 regulates leukocyte adhesion and \u03b22 integrin activation"],"prefix":"10.1093","volume":"111","author":[{"given":"Wei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Medicine, UConn Health , Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan Y","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University , West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University , West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, UConn Health , Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel S","family":"Pachter","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, UConn Health , Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Groisman","sequence":"additional","affiliation":[{"name":"Department of Physics, University of California San Diego , La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Imperioli","sequence":"additional","affiliation":[{"name":"Department of Neurology, UConn Health , Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Wajnsztajn","family":"Yungher","sequence":"additional","affiliation":[{"name":"Department of Neurology, UConn Health , Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Hu","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute of Zhengzhou University, Department of Cardiology, the First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, UConn Health , Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University , West Lafayette, Indiana, USA"},{"name":"Purdue Institute for Inflammation, Immunology, & Infectious Disease, Purdue University , West Lafayette, Indiana, USA"},{"name":"Purdue University Center for Cancer Research, Purdue University , West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichao","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, UConn Health , Farmington, Connecticut, 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