Properties of hydrogen peroxide-induced histamine release from rat mast cells.

Incubation of rat peritoneal mast cells with hydrogen peroxide results in a marked release of histamine. Maximal release is observed with 0.05-0.1 mM H(2)O(2), but higher concentrations of H(2)O(2) instead suppresses the release. Histamine release starts after about 2 min of lag time and reaches a plateau in about 10 min. Hydrogen peroxide-induced release does not exceed 50-60 per cent of total histamine if the incubations are prolonged or additional H(2)O(2) is given at 10 min. This would be explained by the fact that H(2)O(2) causes impairment of the histamine releasing system of mast cells simultaneously with the release of histamine. Hydrogen peroxide-induced release is not due to nonspecific lysis of the cells because lactate dehydrogenase, a cytoplasmic enzyme, is not liberated during the reaction. The reaction requires the presence of Ca(2+), is enhanced by D(2)O and suppressed by colchicine. It is not, however, affected by dibutyryl cAMP or dibutyryl cGMP. No significant alteration of intracellular levels of cyclic AMP and cyclic GMP is observed during the incubation of mast cells with 0.1 mM H(2)O(2). These results indicate that microtubular functions would be involved in the releasing reaction although they are not under the control of cyclic nucleotides. Microscopic observation shows that H(2)O(2)-induced release is accompanied by degranulation.