Studies in experimental eosinophilia. XI. Dependence of eosinophilia, apparently induced by histamine, on acidity

A solution of histamine in saline elicited eosinophil response in both lymph nodes and the blood stream. The lymph node response was not inhibited by the antihistamine, mepyramine maleate, but was inhibited by puromycin. Both the lymph node and the systemic response were essentially abolished when the pH of the solution (5.0 and 4.7, respectively) was brought to neutrality by phosphate buffer. Serum could bring the pH of histamine to neutrality or higher, but the histamine-serum mixture retained in vivo activity, unless the histamine was buffered before addition to the serum. When normal guinea pig gamma-globulin was incubated with histamine, a nondialyzable factor was generated which had the same activity as histamine. Thirteen different amino acids induced lymph node eosinophilia and each was acid in saline solution; when one of them, trytophane, was brought to neutral pH, its activity was considerably reduced. During the period when the circulating level of eosinophils was rising, there was no detectable fall in the bone marrow stores of mature of immature eosinophils. Thus, the activity of histamine, vis-a-vis eosinophils, is nonspecific and is attributable to its acidity. The data suggest that histamine, in the acidic state, generates autoantigens, which, in turn, lead to antibody-mediated eosinophilia in lymph nodes.