Complement-dependent and independent mechanisms in acute antibody-mediated rejection of skin xenografts in the mouse.

Complement dependency of acute antibody-mediated rejection (AAR) was studied in a xenogeneic skin graft model in the mouse. PVG/c rat skin grafted to immunosuppressed mice was acutely destroyed by i.v. administered mouse anti-rat serum on day 7 after grafting. Depression of the hemolytic complement titer in the recipients was indicative for complement consumption during the rejection process. Complete and long-lasting complement depletion induced by treatment with cobra venom factor (COVF) decreased the sensitivity of the grafts to AAR. However, complete protection was not achieved, since high doses of antidonor serum again induced destruction. Similar results were obtained in C5-deficient recipients and in COVF-treated C5-deficient recipients. These results indicated that complement-independent rejection mechanisms were operative. This was further substantiated by the finding that purified noncomplement-fixing IgC1 subclass antibodies were able to elicit mice with a normal complement status was caused by intravascular coagulation without primary involvement of polymorphonuclear leukocytes. In complement-depleted animals an Arthus-like reaction was seen, with dense intravascular accumulation of polymorphonuclear leukocytes (PMNs) that, apparently, were attracted to the graft through complement-independent mechanisms.