Effects of tumor-enhancing IgG2 on macrophage function

Macrophages (M phi) play a significant role in allograft rejection. We investigated whether tumor-enhancing (te) IgG(2) acting as a cytophilic opsonin affects allograft destruction. Our results demonstrate that immune Tennessee Swiss (TS) (H-2(s)) mouse M phi destroyed greater numbers of target C3H(f)/He (H-2(k)) tumor cells than did nonimmune M phi. The percentage of (51)Cr release from labeled tumor cells induced by immune M phi was 39.10 + 3.24% compared to nonimmune M phi 28.0 + 3.87%, while te IgG suppressed cytotoxicity toward C3H(f)/He tumor cells of normal TS M phi as manifested by less isotope release (19.60 + 3.13%) than that produced by normal TS M phi with non-enhancing IgG(2) (39.90 + 5.8%). Rather than facilitating survival of allogeneic fibrosarcoma cells, te IgG(2) alloantibody potentiated their destruction by immune TS M phi (isotope release of 52.90 + 3.46%) compared with that produced by immune M phi alone (39.10 + 3.24%). Cytophilic te IgG(2) on TS M phi was demonstrated with either C3H(f)/He red cells or tumor cells. Electron micrographs of M phi revealed tumor cell ingestion and attachment of ferritin-labeled IgG(2) alloantibody on M phi and target tumor cells. In contrast to protection, te IgG(2) alloantibody facilitates macrophage-mediated allograft destruction.