(276b) 'marker of Self' Proteins on Synthetics - Exploiting the Body's Own System of Distinguishing Foreign from Self

Any particle injected or surface implanted in us or any other mammal must contend with Macrophages that have ? for eons ? swept up invading bacteria, yeast, and other pathogens. At the same time, Macrophages leave our own ?Self' cells alone. The Foreign vs Self difference certainly does NOT reside in steric repulsion by the glycocalyx, which some have argued is well-mimicked by the modern synthetic polymer PEG. We have sought to address how Macrophages specifically recognize Self and to define its physicochemical limits, and we have focused on a cell-surface protein found on all of our own cells. We demonstrate a two-step procedure for recognizing intruders that helps avoid misdirected attacks. In the first step, which is well known, Macrophages adhere and begin engulfing objects studded with antibodies or plasma complement proteins that bind interlopers and will also bind to the body's own cells. However, before a macrophage engulfs its target, it also gropes and checks for the second form of identification on all self cells, the protein CD47. The ~100 aa extracellular domain of CD47 is sufficient to induce a macrophage to disengage a cell from the same species or even a synthetic particle decorated with this domain. We will detail the divergence in Foreign vs Self adhesive signaling mechanisms, the dependence on protein densities, and the length scale dependence for this fundamental facet of immunocompatability.