Tissue reactions to anaphylactic and anaphylactoid stimuli; proteolysis and release of histamine and heparin

Addition of the specific antigen to slices of liver or lung taken from sensitized guinea pigs, or the addition of anaphylactoid agents (tween 20, octadecylamine, morphine, and 48/80) to tissue slices from normal animals, or the perfusion of lung with these agents, has been shown to cause protein breakdown and liberation of histamine and heparin. The dose correlation between these phenomena raises the question of which is the causal event. Suppression of histamine and heparin release by inhibition of proteolysis suggests that the latter is the more fundamental reaction, but the problem probably can not be decided on the basis of present knowledge. Tissue proteolysis induced by the agents investigated in this work results from the action of a protease present in normal tissues as an inactive precursor. Conversion of the proenzyme requires the intervention of a kinase. The tissue kinase seems to be different from the serum kinase which has been shown to be related to complement. Serum kinase, however, also acts on tissue proenzyme and probably plays an important role in tissue reactions as elicited in the intact animal.