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Sickle cell disease (SCD) is a genetic blood disorder in which red blood cells (RBCs) are constantly destroyed in the circulation which generates a highly inflammatory environment that culminates in vascular occlusions. Vaso\u2010occlusion is the hallmark of SCD and a predictor of disease severity. Neutrophils initiate and propagate SCD\u2010related vaso\u2010occlusion through adhesive interactions with the activated and dysfunctional endothelium, sickle RBCs, and platelets, leading to acute and chronic complications that progress to irreversible organ damage and ultimately death. The use of SCD humanized mouse models, in combination with in vivo imaging techniques, has emerged as a fundamental tool to understand the dynamics of neutrophils under complex inflammatory contexts and their contribution to vascular injury in SCD. In this review, we discuss the various mechanisms by which circulating neutrophils sense and respond to the wide range of stimuli present in the blood of SCD patients and mice. We argue that the central role of neutrophils in SCD can be rationalized to develop targets for the management of clinical complications in SCD patients.<\/jats:p>","DOI":"10.1111\/imr.13146","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T17:17:00Z","timestamp":1666027020000},"page":"302-312","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Neutrophils as drivers of vascular injury in sickle cell disease"],"prefix":"10.1111","volume":"314","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4598-1899","authenticated-orcid":false,"given":"Lidiane S.","family":"Torres","sequence":"first","affiliation":[{"name":"Ruth L. and David S. 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