Extracellular histones induce erythrocyte fragility and anemia.

Abstract:

:Extracellular histones have been shown to play an important pathogenic role in many diseases, primarily through their cytotoxicity toward nucleated cells and their ability to promote platelet activation with resultant thrombosis and thrombocytopenia. In contrast, little is known about the effect of extracellular histones on erythrocyte function. We demonstrate in this study that histones promote erythrocyte aggregation, sedimentation, and using a novel in vitro shear stress model, we show that histones induce erythrocyte fragility and lysis in a concentration-dependent manner. Furthermore, histones impair erythrocyte deformability based on reduced passage of erythrocytes through an artificial spleen. These in vitro results were mirrored in vivo with the injection of histones inducing anemia within minutes of administration, with a concomitant increase in splenic hemoglobin content. Thrombocytopenia and leukopenia were also observed. These findings suggest that histones binding to erythrocytes may contribute to the elevated erythrocyte sedimentation rates observed in inflammatory conditions. Furthermore, histone-induced increases in red blood cell lysis and splenic clearance may be a significant factor in the unexplained anemias seen in critically ill patients.

journal_name

Blood

journal_title

Blood

authors

Kordbacheh F,O'Meara CH,Coupland LA,Lelliott PM,Parish CR

doi

10.1182/blood-2017-06-790519

subject

Has Abstract

pub_date

2017-12-28 00:00:00

pages

2884-2888

issue

26

eissn

0006-4971

issn

1528-0020

pii

blood-2017-06-790519

journal_volume

130

pub_type

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