P‐selectin plays a role in haem‐induced acute lung injury in sickle mice

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dc.contributor.author Ghosh, S.
dc.contributor.author Flage, B.
dc.contributor.author Weidert, F.
dc.contributor.author Ofori-Acquah, S.F.
dc.date.accessioned 2019-05-23T10:46:50Z
dc.date.available 2019-05-23T10:46:50Z
dc.date.issued 2019-02
dc.identifier.other https://doi.org/10.1111/bjh.15807
dc.identifier.uri http://ugspace.ug.edu.gh/handle/123456789/30241
dc.description.abstract Acute chest syndrome (ACS) is a major pulmonary complication and a leading cause of death in sickle cell disease (SCD) (Gladwin & Vichinsky, 2008). Extracellular haem has been shown to be independently associated with ACS and vaso‐occlusive crisis (VOC). Severe ACS is frequently preceded by painful VOC and acute intravascular haemolysis (Vichinsky et al, 2000). A rapid drop in baseline haemoglobin (mean decrease of 7·8 g/l) and elevated lactate dehydrogenase reported during ACS development indicates a cardinal role of acute intravascular haemolysis in severe ACS (Vichinsky et al, 1997). Accordingly, infusion of purified haem causes respiratory failure and lethal acute lung injury (ALI) reminiscent of severe ACS in transgenic SCD (SS) mice (Ghosh et al, 2013). P‐selectin, a cell adhesion molecule expressed on activated endothelium and platelets, is implicated in obstructing microvascular flow, causing VOC (Embury et al, 2004) by promoting adhesion of sickle erythrocytes and leucocytes to the endothelial wall (Matsui et al, 2001). Extracellular haem activates endothelial P‐selectin expression, inducing vascular stasis in murine models of SCD (Belcher et al, 2014). A recent trial showed that an anti‐human P‐selectin antibody reduced the frequency of painful events in SCD patients (Ataga et al, 2017), although it could not determine the role of P‐selectin in ACS. This study addresses this knowledge gap and provides mechanistic evidence demonstrating a pathogenic role for P‐selectin in the development of haem‐induced ALI in sickle mice. en_US
dc.language.iso en en_US
dc.publisher British Journal of Haematology en_US
dc.subject P-selectin en_US
dc.subject Acute chest syndrome en_US
dc.subject Haem en_US
dc.subject Sickle cell disease en_US
dc.title P‐selectin plays a role in haem‐induced acute lung injury in sickle mice en_US
dc.type Article en_US

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