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Hemoglobin: a newly recognized binding protein for bacterial endotoxins (LPS)
1Department of Laboratory Medicine, University of California School of Medicine, San Francisco.
Progress in Clinical and Biological Research
|January 1, 1994
Summary
Purified hemoglobin (Hb) resuscitation fluid can form complexes with bacterial endotoxins (lipopolysaccharide, LPS). This interaction enhances LPS biological activity, potentially explaining Hb-induced toxicity and sepsis complications.
Area of Science:
- Biochemistry
- Toxicology
- Immunology
Background:
- Cell-free hemoglobin (Hb) administration for resuscitation is linked to organ toxicities.
- These toxicities resemble those caused by bacterial endotoxins like lipopolysaccharide (LPS).
Purpose of the Study:
- To investigate the potential role of LPS in Hb-induced toxicity.
- To examine the formation and biological consequences of LPS-Hb complexes.
Main Methods:
- Complex formation assessed via ultrafiltration, density centrifugation, and ethanol precipitation.
- Biological activity of LPS-Hb complexes evaluated using Limulus amebocyte lysate (LAL) assay, and human mononuclear cell and endothelial cell tissue factor release.
Main Results:
- Evidence of LPS-Hb complex formation was demonstrated using multiple techniques.
- LPS-Hb complexation altered LPS physical characteristics and significantly enhanced its biological activity.
- Enhanced LPS activity included increased LAL activation and greater tissue factor release.
Conclusions:
- Hemoglobin acts as an endotoxin-binding protein, forming complexes with LPS.
- LPS-Hb complexation potentiates the biological effects of LPS, suggesting a mechanism for Hb toxicity.
- Erythrocyte hemolysis may exacerbate LPS-related morbidity during sepsis by releasing Hb.