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Molecular physiology

Haemoglobin scavenger

Naturevolume 409page141 (2001) | Download Citation

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Normally, ageing red blood cells approaching the end of their 120-day lifespan are degraded in the bone marrow, liver or spleen. In some circumstances, however — such as during infection with malaria or in some autoimmune disorders — red cells may burst within blood vessels. Haemoglobin (Hb) released from ruptured red cells can be toxic unless cleared rapidly from the circulation. Haptoglobin (Hp), a protein found in blood plasma, binds free Hb, but the events that lead to removal of the Hp–Hb complex from the blood have been elusive — until now.

Elsewhere in this issue (Nature 409, 198–201; 2001), Søren K. Moestrup and colleagues describe how they detected a receptor protein that clears the Hp–Hb complex from blood. They identify the protein as CD163, known to be expressed only on the surface of tissue macrophages and monocytes — white blood cells — and to be involved in inflammation. It seems that the Hp–Hb complex acts as a 'come hither' signal to patrolling macrophages, detected through their CD163 antennae. The Hp–Hb complex is then engulfed by the macrophage and digested to release haem (see graphic).

Figure 1
Figure 1

S. K. MOESTRUP

The Hp–Hb complex is engulfed by the macrophage and digested to release haem.

These findings reveal an intriguing link between iron metabolism and the immune system. The authors speculate that the Hp–Hb complex, like antibodies, may crosslink several CD163 molecules on the surface of macrophages, triggering an internal signalling cascade that results in increased secretion of anti-inflammatory cytokine molecules. Moestrup and colleagues also propose that different inherited human variants of Hp in complex with Hb may have different anti-inflammatory potency. But it is also feasible that the Hp–Hb complex responds to immune processes. CD163 and Hp are upregulated in response to factors such as interleukin-6, seen in the early, acute phase of inflammation, suggesting that this may be a means of enhancing Hb clearance during inflammatory conditions.

Further evidence is needed. But it is tempting to speculate that variations in Hp and CD163, or pertubations of their function, may be involved in autoimmune disorders such as systemic lupus erythematosus, and in abnormal iron metabolism.

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https://doi.org/10.1038/35051680

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