Fig. 6. Antibody-dependent and -independent xenorecognition of macrophages. Monocytes or macrophages can trigger the destruction of porcine cells through two immune mechanisms. In the antibody-dependent process, macrophages are activated via FcR-mediated signaling during their interaction with cells coated by xenoreactive antibodies. In contrast, in the antibody-independent process, monocytes are activated through direct recognition of xenogeneic antigens, such as α-Gal, via cell surface receptor, such as galectin-3. Molecular incompatibility of myeloid inhibitory molecules, such as CD47 and CD200, between pigs and humans contributes to weak negative feedback on macrophage activation and leads to overactivation of macrophages after xenotransplantation. α-Gal, α-galactosidase; FcR, Fc receptor; DAMP, danger-associated molecular pattern; TLR, Toll-like receptor; SIRPα, signal regulatory protein alpha.