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Comment
. 2014 Jun 12;123(24):3689-90.
doi: 10.1182/blood-2014-03-563874.

Erythroid DAMPs drive inflammation in SCD

Mark T Gladwin  1 , Solomon F Ofori-Acquah  1
Affiliations
Comment

Erythroid DAMPs drive inflammation in SCD

Mark T Gladwin et al. Blood. .

Abstract

In this issue of Blood, Chen et al show that heme is released during erythrocyte hemolysis in sickle cell disease, activating the innate immune response and triggering the release of neutrophil extracellular traps (NETs) to promote lung injury.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Hemolysis releases erythroid DAMP molecules to drive vascular injury and sterile inflammation, which contribute to the pathogenesis of sickle cell disease. Hemolysis releases cell free hemoglobin (Hb), which is normally scavenged by haptoglobin and CD163. Free hemoglobin reacts with and scavenges NO via the dioxygenation reaction and also reacts with hydrogen peroxide to generate hydroxyl radicals via the Fenton reaction. This process leads to endothelial dysfunction and pathological vascular remodeling. Oxidized hemoglobin releases free heme, which can trigger a sterile inflammatory reaction involving TLR4 activation, and stimulates neutrophils to release NETs. These inflammatory events are proposed to cause vasoocclusion and acute chest syndrome in sickle cell disease. There are several potential therapies using the indicated agents (shown in red text) that target multiple stages of this proposed pathophysiological pathway. RBC, red blood cell. Professional illustration by Debra T. Dartez.
See this image and copyright information in PMC

Comment on

References

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