Inhibition of anaphylactic histamine release by Forssman antiserum. II. Mechanism of inhibition.

Abstract

The mechanism was studied of the inhibitory effect of IgG Forssman antibody on anaphylactic sensitization in the guinea pig lung. Two possibilities were considered to explain the inhibitory effect: either the Forssman antibody-antigen interaction occurred on the mast cell, allowing the F(ab′)<sub>2</sub> portion to interfere with the Fc receptor(s) for anaphylactic antibody; or the interaction took place adjacent to the mast cell allowing the Fc portion to occupy the receptors for anaphylactic antibody. These studies were made possible in part by developing a method for preparing mast cell suspensions from guinea pig lung. The mast cells were viable but released histamine only on treatment with compound 48/80 and not with anaphylatoxin, soluble immune complexes or with active or passive anaphylactic sensitization. Mast cells incubated with Forssman antibody and complement showed no evidence of injury as judged by electron microscopy, suggesting that they did not contain Forssman antigen. The absence of Forssman antigen from mast cells was substantiated further by studies of mixed agglutination and fluorescence microscopy. Also, pepsin digestion of Forssman antibody resulted in a loss of the ability to inhibit the histamine-releasing activity of soluble immune complexes, indicating that the F(ab′)<sub>2</sub> portion alone was not sufficient to sustain the inhibitory process. It was concluded that the inhibitory effect of IgG Forssman antibody was due to union with interstitial Forssman antigen adjacent to mast cells, allowing the Fc portion of the Forssman antibody to irreversibly occupy the mast cell Fc receptor(s) for anaphylactic antibody.