Red blood cells mediate the onset of thrombosis in the ferric chloride murine model

Justin D Barr; Anil K Chauhan; Gilbert V Schaeffer; Jessica K Hansen; David G Motto

doi:10.1182/blood-2012-11-468983

Back

Red blood cells mediate the onset of thrombosis in the ferric chloride murine model

Journal article

Open access

Peer reviewed

Red blood cells mediate the onset of thrombosis in the ferric chloride murine model

Justin D Barr, Anil K Chauhan, Gilbert V Schaeffer, Jessica K Hansen and David G Motto

Blood, Vol.121(18), pp.3733-3741

05/02/2013

DOI: 10.1182/blood-2012-11-468983

PMCID: PMC3643770

PMID: 23343833

Files and links (1)

url

https://doi.org/10.1182/blood-2012-11-468983View

Published (Version of record) Open Access

Abstract

The ferric chloride model does not result in endothelial denudation. In the ferric chloride model, platelets bind to endothelial-associated RBC-derived material rather than to the endothelial surface. Application of ferric chloride (FeCl 3 ) to exposed blood vessels is widely used to initiate thrombosis in laboratory mice. Because the mechanisms by which FeCl 3 induces endothelial injury and subsequent thrombus formation are little understood, we used scanning electron and brightfield intravital microscopy to visualize endothelial damage and thrombus formation occurring in situ. Contrary to generally accepted belief, FeCl 3 does not result in appreciable subendothelial exposure within the time frame of thrombosis. Furthermore, the first cells to adhere to FeCl 3 -treated endothelial surfaces are red blood cells (RBCs) rather than platelets. Energy dispersive x-ray spectroscopy demonstrated that ferric ions predominantly localize to endothelial-associated RBCs and RBC-derived structures rather than to the endothelium. With continuing time points, RBC-derived structures rapidly recruit platelets, resulting in large complexes that subsequently enlarge and coalesce, quickly covering the endothelial surface. Further studies demonstrated that neither von Willebrand factor nor platelet glycoprotein Ib-α receptor (GPIb-α) is required for RBCs to adhere to the endothelium, and that deficiency of GPIb-α greatly abrogated the recruitment of platelets to the endothelial-associated RBC material. These findings illuminate the mechanisms of FeCl 3 -mediated thrombosis and reveal a previously unrecognized ability of RBCs to participate in thrombosis by mediating platelet adhesion to the intact endothelial surface.

Thrombosis and Hemostasis

Details

Title: Subtitle: Red blood cells mediate the onset of thrombosis in the ferric chloride murine model
Creators: Justin D Barr - Department of Internal Medicine
Anil K Chauhan - Department of Internal Medicine
Gilbert V Schaeffer - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA
Jessica K Hansen - Department of Biomedical Engineering, University of Iowa College of Engineering, Iowa City, IA; and
David G Motto - Department of Internal Medicine
Resource Type: Journal article
Publication Details: Blood, Vol.121(18), pp.3733-3741
DOI: 10.1182/blood-2012-11-468983
PMID: 23343833
PMCID: PMC3643770
NLM abbreviation: Blood
ISSN: 0006-4971
eISSN: 1528-0020
Publisher: American Society of Hematology
Grant note: 1R01HL106495-01 / National Institutes of Health
Language: English
Date published: 05/02/2013
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094555302771

Metrics

24 Record Views

138 Times Cited - Web of Science