THE MECHANISM OF ANAPHYLAXIS. I. PRODUCTION AND BIOLOGICAL PROPERTIES OF 'MAST CELL SENSITIZING' ANTIBODY

Abstract

In addition to the usual serum precipitating antibody, immunized rats produce a thermolabile antibody that is able to sensitize mast cells and cause damage to these cells on reacting with the specific antigen. Due to this property this antibody is called `mast cell sensitizing' antibody (MCSAb). Like human reagins, it is destroyed by heating at 56° and when injected into homologous skin will remain at the site of injection for as long as 1 month. In contrast, the antibody disappears very quickly from serum when injected into recipient rats. Although its production can be induced in various ways, the administration of Bordetella pertussis organisms along with the antigen is particularly effective. MCSAb seems to be the product of a primary response, since its production is prevented or very much reduced by previous or additional contacts with antigen.

The mechanism of passive sensitization of mast cells with MCSAb was studied by incubating pieces of rat mesentery with antigen in vitro, using antigen-induced mast cell damage or histamine release as a measure of sensitization. Sensitization increases with time of contact between cells and antibody and can attain a maximum within the first few minutes depending upon antibody concentration. Sensitizations at 37° and 4° proceed at about the same speed. Nonspecific γ-globulin inhibits sensitization with MCSAb when used in large amounts. Rabbit, rat, human and bovine γ-globulin slowed down sensitization, whereas horse γ-globulin was without effect. Sensitization with MCSAb can be completely reversed by washing the sensitized mesentery in Tyrode's solution. The time required to remove MCSAb by washing was inversely proportional to the time of contact between cells and antiserum during sensitization. Anaphylactic phenomena induced with MCSAb seem to be primarily due to histamine and 5-hydroxytryptamine release. The possibility of a relationship between the methods of immunization leading to the production of mast cell sensitizing antibody and the establishment of a delayed hypersensitivity is considered.