Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/234935
Title: Extracellular haemoglobin upregulates and binds to tissue factor on macrophages: Implications for coagulation and oxidative stress
Authors: Bahl, Neha 
Winarsih, Imelda 
Tucker-Kellogg, Lisa 
Ding, Jeak Ling 
Keywords: Science & Technology
Life Sciences & Biomedicine
Hematology
Peripheral Vascular Disease
Cardiovascular System & Cardiology
Haemolysis
lipopolysaccharide
sepsis
oxidative stress
co-evolution of haemoglobin and tissue factor
SICKLE-CELL-DISEASE
PROCOAGULANT ACTIVITY
ENDOTHELIAL-CELLS
BACTERIAL-ENDOTOXIN
BLOOD-COAGULATION
FACTOR EXPRESSION
DISULFIDE BOND
LIPID-A
ACTIVATION
LIPOPOLYSACCHARIDE
Issue Date: 1-Jan-2014
Publisher: GEORG THIEME VERLAG KG
Citation: Bahl, Neha, Winarsih, Imelda, Tucker-Kellogg, Lisa, Ding, Jeak Ling (2014-01-01). 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
URI: https://scholarbank.nus.edu.sg/handle/10635/234935
ISSN: 0340-6245
2567-689X
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