Please use this identifier to cite or link to this item:
Title: Extracellular haemoglobin upregulates and binds to tissue factor on macrophages: Implications for coagulation and oxidative stress
Authors: Bahl, N.
Winarsih, I. 
Tucker-Kellogg, L. 
Ding, J.L. 
Keywords: Co-evolution of haemoglobin and tissue factor
Oxidative stress
Issue Date: 10-Oct-2013
Citation: Bahl, N., Winarsih, I., Tucker-Kellogg, L., Ding, J.L. (2013-10-10). Extracellular haemoglobin upregulates and binds to tissue factor on macrophages: Implications for coagulation and oxidative stress. Thrombosis and Haemostasis 111 (1) : 67-78. ScholarBank@NUS Repository.
Abstract: The mechanisms of crosstalk between haemolysis, coagulation and innate immunity are evolutionarily conserved from the invertebrate haemocyanin to the vertebrate haemoglobin (Hb). In vertebrates, extracellular Hb resulting from haemolytic infections binds bacterial lipopolysaccharide (LPS) to unleash the antimicrobial redox activity of Hb. Because bacterial invasion also upregulates tissue factor (TF), the vertebrate coagulation initiator, we asked whether there may be functional interplay between the redox activity of Hb and the procoagulant activity of TF. Using real-time PCR, TF-specific ELISA, flow cytometry and TF activity assay, we found that Hb upregulated the expression of functional TF in macrophages. ELISA, flow cytometry and immunofluorescence microscopy showed binding between Hb and TF, in isolation and in situ. Bioinformatic analysis of Hb and TF protein sequences showed co-evolution across species, suggesting that Hbβ binds TF. Empirically, TF suppressed the LPS-induced activation of Hb redox activity. Furthermore, Hb desensitised TF to the effects of antioxidants like glutathione or serum. This bi-directional regulation between Hb and TF constitutes a novel link between coagulation and innate immunity. In addition, induction of TF by Hb is a potentially central mechanism for haemolysis to trigger coagulation. © Schattauer 2014.
Source Title: Thrombosis and Haemostasis
ISSN: 03406245
DOI: 10.1160/TH13-03-0220
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Feb 20, 2020


checked on Feb 20, 2020

Page view(s)

checked on Feb 22, 2020

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.