The antigen-induced release of SRS-A and histamine was studied in the guinea pig and rat using whole and fractionated antiserum preparations.

Guinea pig 7Sγ1-antibody sensitized sliced guinea pig lung tissue for antigen-induced release of both SRS-A and histamine; neither substance was released from lung tissue prepared with 7Sγ1-antibody.

Rats injected intraperitoneally with hyperimmune rabbit or rat antiserum released only SRS-A in significant amounts when challenged with antigen by the same route. A definite time interval between the injection of antiserum and challenge with antigen was required for optimal release of SRS-A.

Fractionation of rat antiserum demonstrated that the immunoglobulin responsible for most of the SRS-A release from rat peritoneal tissue was a γG-antibody or fraction thereof. Acting in this capacity, the γG-antibody or its subfraction may be considered a second type of homocytotropic antibody. Fractions of rat antisera containing the first type of homocytotropic antibody, i.e. antibody mediating release of histamine and serotonin, prepared peritoneal tissues for the release of large amounts of these pharmacological agents and only small amounts of SRS-A.

Two different mechanisms for the production of PCA lesions in the rat were considered. One of these involves the antigen-induced release of histamine and serotonin from mast cells sensitized by homocytotropic antibody. This reaction has an optimal latent period of 24–72 hr. The second mechanism involves the local combination of antigen with "hyperimmune" heterologous or homologous antisera. This reaction can be elicited after a latent period of 4 but not 24 hr; host complement and leukocyte lysosomal enzymes, as well as SRS-A, may be involved.

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