Activation of human complement by rat peritoneal mast cells and its inhibition by a rat serum factor

The effects of normal sera from humans, rats, and guinea pigs on unsensitized rat peritoneal mast cells were studied in vitro. Five to 20% fresh human sera induced mast cell death and substantial histamine release. The factor was heat labile. Neither hereditary C3-deficient sera nor experimentally C1q-depleted sera showed cytotoxicity. The CH50 activity of human serum was decreased to about one half after a 15-min incubation with 2 X 10(6) mast cells/ml at 37 degrees C. The cytotoxic activity and CH50 reduction were completely eliminated by an addition of 10 mM Mg-EGTA to the serum. These data demonstrated that unsensitized rat mast cells served as both the initiator and target of complement activity when human serum was used as a complement source. Requirements of both Ca++ and C1q suggested the activation of the classical pathway of complement. Fresh 5-20% sera from rats and guinea pigs, on the other hand, showed neither cytotoxicity nor CH50 reduction. Furthermore, these sera strongly inhibited the human serum-induced reaction. The latter results indicated the presence of a modulating factor in rat and guinea pig sera, which inhibits mast cell associated complement activation.