(623ab) CD47 Inhibit the Immune System Response Against Nanoparticles In Vivo | AIChE

(623ab) CD47 Inhibit the Immune System Response Against Nanoparticles In Vivo

Authors 

Discher, D. E. - Presenter, University of Pennsylvania

A major challenge for injecting particles or implanting biomaterials into the body is that they activate immune cells such as macrophages, the cells that normally function to clear invading pathogens. Interestingly, macrophages have a surface receptor mechanism which prevents them from phagocytosing our own cells. During initial macrophage engulfment, macrophages recognize foreign and self targets because they both have antibodies or plasma complement proteins on their surface.  However, before the macrophage engulfs the target, cells are checked for the presence of the surface protein CD47.  CD47 is recognized by the receptor SIRPa on macrophages which inhibits phagocytosis, and when we attach a 100 aa extracellular component of CD47 to micro- and nano-sized particle, we demonstrate, in vitro, that this sufficient to inhibit phagocytosis of these small particles. Now we are focusing our efforts on understanding how these results are consistent with in vivo systems. In vivo, we are currently testing whether nanoparticles that have surface immobilized hCD47 will not be phagocytosed in nobese diabetic (NOD) mice, because we tested that hCD47 actually bind to this mSirpa strain.  We will detail the dependence on protein densities and the length scale dependence for this fundamental facet of immunocompatability.