Macrophages are white blood cells that "scavenge" a broad range of cellular components and play a central role in orchestrating the immune defence in autoimmune diseases and infections. Macrophages express abundantly the CD163 receptor which normally binds and internalizes hemoglobin-haptoglobin complexes. Cytoguide exploits CD163 uptake of conjugate drugs for specific targeting of macrophages.


Monocytes/macrophages express on their surface in abundant measure the CD163 protein, which is the established receptor for scavenging hemoglobin. The receptor acts in concert with haptoglobin that binds to hemoglobin prior to recognition of the complex by CD163. Binding of the haptoglobin-hemoglobin complex leads to degradation of the ligand whereas the receptor recycles .


The heme moiety of hemoglobin is transformed to the yellow pigment bilirubilin, which is released from the macrophage. The entire pathway haptoglobin, CD163 and the enzyme of heme metabolization are upregulated by IL-6, a main mediator of the acute phase response on infection. CD163 is constitutively internalized thus indicating that it in principle will transport any substance bound to it. So far it has been shown that it can transport haptoglobin-hemoglobin-complexes as well as antibodies into the cell.



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