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Calorimetric Characterisation of the Binding Reaction Between Human Ferric Haemoglobins and Haptoglobin to Develop a Drug for Removal of Cell-Free Haemoglobin

Ratanasopa, Khuanpiroon LU and Bulow, Leif LU (2022) In Advances in Experimental Medicine and Biology 1395. p.341-345
Abstract

High levels of cell-free haemoglobin (Hb) may occur in plasma as a consequence of e.g., pathological haemolysis or blood transfusion. These Hb molecules can be removed from blood circulation by forming a complex with the acute-phase protein haptoglobin (Hp) and thereby can also the intrinsic toxicity of free Hb be limited. In this study it is shown that ferric HbA, HbF, HbE and HbS, respectively, all bind firmly to Hp at 25 °C. By using isothermal titration calorimetry (ITC), it is demonstrated that ferric HbF has higher affinity to Hp (Ka = 2.79 ± 0.29 ×109 M−1) compared with HbA and HbS (1.91 ± 0.24 ×109 M−1) and 1.41 ± 0.34 ×109 M−1 for HbA and HbS, respectively. In... (More)

High levels of cell-free haemoglobin (Hb) may occur in plasma as a consequence of e.g., pathological haemolysis or blood transfusion. These Hb molecules can be removed from blood circulation by forming a complex with the acute-phase protein haptoglobin (Hp) and thereby can also the intrinsic toxicity of free Hb be limited. In this study it is shown that ferric HbA, HbF, HbE and HbS, respectively, all bind firmly to Hp at 25 °C. By using isothermal titration calorimetry (ITC), it is demonstrated that ferric HbF has higher affinity to Hp (Ka = 2.79 ± 0.29 ×109 M−1) compared with HbA and HbS (1.91 ± 0.24 ×109 M−1) and 1.41 ± 0.34 ×109 M−1 for HbA and HbS, respectively. In addition, the affinity constant for HbE is slightly lower than the other haemoglobins (0.47 ± 0.40 ×109 M−1). Since Hp shows a general and high affinity to all Hb variants tested, it can be concluded that Hp may be useful as a therapeutic agent for several different haemolytic conditions by intravenous injection.

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Please use this url to cite or link to this publication:
author
and
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
Hb variants, Isothermal titration calorimetry, Pathological haemolysis, Sickle cell anemia
host publication
Oxygen Transport to Tissue XLIII
series title
Advances in Experimental Medicine and Biology
volume
1395
pages
5 pages
publisher
Springer Gabler
external identifiers
  • pmid:36527659
  • scopus:85144585279
ISSN
2214-8019
0065-2598
ISBN
978-3-031-14189-8
978-3-031-14190-4
DOI
10.1007/978-3-031-14190-4_55
language
English
LU publication?
yes
id
33302634-6125-4899-a076-ad61214e9cc1
date added to LUP
2023-01-16 14:07:30
date last changed
2025-02-07 02:19:11
@inbook{33302634-6125-4899-a076-ad61214e9cc1,
  abstract     = {{<p>High levels of cell-free haemoglobin (Hb) may occur in plasma as a consequence of e.g., pathological haemolysis or blood transfusion. These Hb molecules can be removed from blood circulation by forming a complex with the acute-phase protein haptoglobin (Hp) and thereby can also the intrinsic toxicity of free Hb be limited. In this study it is shown that ferric HbA, HbF, HbE and HbS, respectively, all bind firmly to Hp at 25 °C. By using isothermal titration calorimetry (ITC), it is demonstrated that ferric HbF has higher affinity to Hp (Ka = 2.79 ± 0.29 ×10<sup>9</sup> M<sup>−1)</sup> compared with HbA and HbS (1.91 ± 0.24 ×10<sup>9</sup> M<sup>−1)</sup> and 1.41 ± 0.34 ×10<sup>9</sup> M<sup>−1</sup> for HbA and HbS, respectively. In addition, the affinity constant for HbE is slightly lower than the other haemoglobins (0.47 ± 0.40 ×10<sup>9</sup> M<sup>−1</sup>). Since Hp shows a general and high affinity to all Hb variants tested, it can be concluded that Hp may be useful as a therapeutic agent for several different haemolytic conditions by intravenous injection.</p>}},
  author       = {{Ratanasopa, Khuanpiroon and Bulow, Leif}},
  booktitle    = {{Oxygen Transport to Tissue XLIII}},
  isbn         = {{978-3-031-14189-8}},
  issn         = {{2214-8019}},
  keywords     = {{Hb variants; Isothermal titration calorimetry; Pathological haemolysis; Sickle cell anemia}},
  language     = {{eng}},
  pages        = {{341--345}},
  publisher    = {{Springer Gabler}},
  series       = {{Advances in Experimental Medicine and Biology}},
  title        = {{Calorimetric Characterisation of the Binding Reaction Between Human Ferric Haemoglobins and Haptoglobin to Develop a Drug for Removal of Cell-Free Haemoglobin}},
  url          = {{http://dx.doi.org/10.1007/978-3-031-14190-4_55}},
  doi          = {{10.1007/978-3-031-14190-4_55}},
  volume       = {{1395}},
  year         = {{2022}},
}