"Marker of self" CD47: from erythrocyte to drug delivery

CD47 on erythrocytes has been shown previously to act as a "marker of self" with SIRP-alpha on macrophages. This study examines the functional role of CD47 in the erythrocyte membrane with respect to both cytoskeletal attachment and association with other surface proteins. CD47 was shown to have a fractional, but significant cytoskeletal connectivity on normal and Rh_nun cells. Additionally, CD47 was shown to colocalize with Rh proteins but not with other cytoskeletally attached proteins, Glycophorin C and Band 3. This suggests that CD47 is independently connected to the underlying cytoskeleton, ensuring that an immobile fraction of CD47 remains equally distributed peripherally at all times. The unconnected fraction could then be recruited to reinforce or amplify this "self" signal. In parallel studies, CD47\´s IgV domain, which is hypothesized to be the key signaling moiety, was expressed on the surface of yeast. Upon contact with neutrophils in plasma, wild type yeast were readily phagocytosed, whereas IgV-CD47+ yeast show dramatically reduced neutrophil activation and phagocytosis. These fundamental insights into CD47\´s integration into the membrane as well as its role in immune system avoidance can further be utilized for biomimetic, proactively stealth drug delivery systems.