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Microvascular Stasis Inhibition By Hemopexin in the Townes Mouse Model of Sickle Cell Disease
- Source :
- Blood; November 2020, Vol. 136 Issue: 1, Number 1 Supplement 1 p9-9, 1p
- Publication Year :
- 2020
-
Abstract
- Polymerization of hemoglobin-S (HbS) in the deoxy conformation shortens the lifespan of sickle red blood cells and promotes intravascular and extravascular hemolysis. When sickle red blood cells are lysed intravascularly, HbS is released into the vascular space where it can consume nitric oxide and be oxidized to higher oxidative forms. During these reactions, ferric (Fe3+) HbS is formed, which readily releases heme. The released heme can activate the innate immune pattern recognition receptor toll-like receptor 4 (TLR4) on endothelium, leading to P-selectin expression, NF-ĸB activation, and microvascular stasis in sickle cell disease (SCD) mice with implanted dorsal skin-fold chambers (DSFCs). Heme-induced TLR4 signalling and stasis are blocked by administering hemopexin with the heme.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 136
- Issue :
- 1, Number 1 Supplement 1
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs57339340
- Full Text :
- https://doi.org/10.1182/blood-2020-140236