Mechanisms of immunologic injury of rat peritoneal mast cells. II. Complement requirement and phosphonate ester inhibition of release of histamine by rabbit anti-rat gamma globulin.

There is an absolute requirement for C'1, C'2, C'4, C'3, and C'5 in releasing histamine from rat peritoneal mast cells sensitized with rabbit anti-rat gamma globulin. This conclusion is based upon the restoration of histamine-releasing capacity by adding highly purified complement components to sera deficient in one or more of these components. Of special advantage was the availability of sera from humans with inborn or acquired deficiencies in a single component. The p-nitrophenyl ethyl phosphonates block this reaction by inhibiting an antigen-antibody-activated esterase which exists in a phosphonate resistant precursor state until activated by the interaction of the sensitized mast cell and serum complement. There is almost complete disparity between the ability of the phosphonates to inhibit complement-dependent histamine release by rabbit anti-RGG and to inactivate C'1a. Even though C'1a is required for complement-dependent histamine release by rabbit anti-RGG, this is not the esterase being blocked by the phosphonates under the experimental conditions used. The pattern of inhibition by the phosphonates of the antigen-antibody-activated esterase required for complement-dependent, noncytotoxic histamine release is remarkably similar to that of the esterase required for homocytotropic antibody-mediated histamine release. One possible implication is that these two quite different modes of carrying out antigen-antibody-induced histamine release from rat peritoneal mast cells lead to activation of the same esterase and share a common pathway.