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Globin attenuates the innate immune response to endotoxin
Huan Yang1, Haichao Wang, Thomas R Bernik
1Laboratory of Biomedical Science, North Shore University Hospital-New York University School of Medicine, New York 11030, USA.
Shock (Augusta, Ga.)
|June 19, 2002
Summary
Hemoglobin binds endotoxins (lipopolysaccharide; LPS) and enhances immune responses. However, globin alone suppresses tumor necrosis factor (TNF) synthesis, indicating the heme-iron part of hemoglobin is key to immune synergy.
Area of Science:
- Immunology
- Biochemistry
Background:
- Hemoglobin binds endotoxins (lipopolysaccharide; LPS), enhancing innate immune responses and cytokine release.
- This synergy is implicated in various clinical conditions with elevated hemoglobin levels, such as post-transfusion or trauma.
Purpose of the Study:
- To investigate the molecular basis of hemoglobin-LPS synergy.
- To determine the specific role of globin versus the heme-iron moiety in macrophage responses to LPS.
Main Methods:
- Testing the effects of globin on LPS-stimulated murine and human macrophage cultures.
- Analyzing LPS-globin binding using non-denaturing electrophoresis and the Limulus assay.
- Assessing the impact of iron supplementation on cytokine release.
Main Results:
- Globin suppressed tumor necrosis factor (TNF) synthesis in LPS-stimulated macrophages.
- Direct evidence of LPS-globin binding was observed.
- Iron supplementation significantly increased interleukin-1beta-induced TNF release.
- Globin administration protected mice against LPS-induced lethality and bacterial infection.
Conclusions:
- The heme-iron moiety of hemoglobin, not LPS binding to globin, enhances macrophage responses to LPS.
- This finding clarifies the mechanism behind hemoglobin's role in innate immunity and endotoxin recognition.