Abstract:
:Intravascular hemolysis describes the relocalization of heme and hemoglobin (Hb) from erythrocytes to plasma. We investigated the concept that erythrocyte membrane microparticles (MPs) concentrate cell-free heme in human hemolytic diseases, and that heme-laden MPs have a physiopathological impact. Up to one-third of cell-free heme in plasma from 47 patients with sickle cell disease (SCD) was sequestered in circulating MPs. Erythrocyte vesiculation in vitro produced MPs loaded with heme. In silico analysis predicted that externalized phosphatidylserine (PS) in MPs may associate with and help retain heme at the cell surface. Immunohistology identified Hb-laden MPs adherent to capillary endothelium in kidney biopsies from hyperalbuminuric SCD patients. In addition, heme-laden erythrocyte MPs adhered and transferred heme to cultured endothelial cells, inducing oxidative stress and apoptosis. In transgenic SAD mice, infusion of heme-laden MPs triggered rapid vasoocclusions in kidneys and compromised microvascular dilation ex vivo. These vascular effects were largely blocked by heme-scavenging hemopexin and by the PS antagonist annexin-a5, in vitro and in vivo. Adversely remodeled MPs carrying heme may thus be a source of oxidant stress for the endothelium, linking hemolysis to vascular injury. This pathway might provide new targets for the therapeutic preservation of vascular function in SCD.
journal_name
Bloodjournal_title
Bloodauthors
Camus SM,De Moraes JA,Bonnin P,Abbyad P,Le Jeune S,Lionnet F,Loufrani L,Grimaud L,Lambry JC,Charue D,Kiger L,Renard JM,Larroque C,Le Clésiau H,Tedgui A,Bruneval P,Barja-Fidalgo C,Alexandrou A,Tharaux PL,Boulanger CMdoi
10.1182/blood-2014-07-589283subject
Has Abstractpub_date
2015-06-11 00:00:00pages
3805-14issue
24eissn
0006-4971issn
1528-0020pii
blood-2014-07-589283journal_volume
125pub_type
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