The Journal of experimental medicine
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The quantitative release of histamine by specific antigen from perfused, chopped, sensitized guinea pig lung has been used to study the effect of peptidase substrates and inhibitors on the anaphylactic reaction. The anaphylactic release of histamine is prevented by chymotrypsin substrates and inhibitors but not by trypsin, carboxypeptidase, or leucine aminopeptidase substrates or the soybean trypsin inhibitor. The chymotrypsin substrates and inhibitors appear to be acting on an antigen-antibody-activated step because these substances fail to inhibit if the tissue is washed free of them prior to antigen addition, and because there is complete desensitization of the tissue without histamine release when the antigen is added in the presence of these inhibitors. ⋯ This indicates that diisopropylfluophosphate must be acting exclusively on an enzyme which exists in lung tissue in a precursor form resistant to diisopropylfluophosphate until activated by the antigen-antibody interaction. Thiol alkylating or oxidizing agents also prevent the anaphylactic release of histamine, but in contrast to the situation with diisopropylfluophosphate and the other chymotrypsin inhibitors, the phase of the anaphylactic reaction inhibited by N-ethylmaleimide is available prior to the antigen-antibody interaction. The similarities and differences between immune hemolysis and anaphylaxis in chopped guinea pig lung are considered in detail.