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Reasoning that genetic models can provide an orthogonal and direct system for the mechanistic study of CD11b agonism, we present in this study, to our knowledge, a novel knock-in model of constitutive active CD11b in mice. We genetically targeted the Itgam gene (which codes for CD11b) to introduce a point mutation that results in the I332G substitution in the protein. The I332G mutation in CD11b promotes an active, higher-affinity conformation of the ligand-binding I\/A-domain (CD11b \u03b1A-domain). In vitro, this mutation increased adhesion of knock-in neutrophils to fibrinogen and decreased neutrophil chemotaxis to a formyl\u2013Met\u2013Leu\u2013Phe gradient. In vivo, CD11bI332G animals showed a reduction in recruitment of neutrophils and macrophages in a model of sterile peritonitis. This genetic activation of CD11b also protected against development of atherosclerosis in the setting of hyperlipidemia via reduction of macrophage recruitment into atherosclerotic lesions. Thus, our animal model of constitutive genetic activation of CD11b can be a useful tool for the study of integrin activation and its potential contribution to modulating leukocyte recruitment and alleviating different inflammatory diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1901402","type":"journal-article","created":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T16:40:19Z","timestamp":1600274419000},"page":"2545-2553","source":"Crossref","is-referenced-by-count":11,"title":["A Genetic Model of Constitutively Active Integrin CD11b\/CD18"],"prefix":"10.1093","volume":"205","author":[{"given":"Laisel","family":"Martinez","sequence":"first","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-8478","authenticated-orcid":false,"given":"Xiaobo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gioser","family":"Ramos-Echazabal","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-1369","authenticated-orcid":false,"given":"Hafeez","family":"Faridi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Chicago State University , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary M","family":"Zigmond","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, Leonard M. Miller School of Medicine, University of Miami , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nieves","family":"Santos Falcon","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana R","family":"Hernandez","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serene A","family":"Shehadeh","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omaida C","family":"Velazquez","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-2550","authenticated-orcid":false,"given":"Vineet","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto I","family":"Vazquez-Padron","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Leonard M. 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