Immunoglobulin E-mediated release of a kininogenase from purified human lung mast cells

Certain manifestations of the allergic response, such as vasodilation and edema, may be attributed to the involvement of kinins, but, as yet, little data exist to show how these peptides could be produced during IgE-mediated events. We now report that purified human lung mast cells contain a kininogenase that is released in a dose-dependent fashion by anti-IgE. Release of kinin-generating activity parallels that of histamine and, like histamine release, kininogenase release is temperature-dependent. Kininogenase release also parallels increasing histamine release when mast cells of increasing size are stimulated with an optimal level of anti-IgE. Finally, when mast cells of greater than 99% purity were optimally challenged, kininogenase activity again paralleled histamine levels in the release supernatant and residual cell pellet. The mast cell kininogenase appears to be a preformed mediator in that it occurs in lysates of unstimulated mast cells of greater than 99% purity. Optimal generation of kinin from highly purified human low molecular weight kininogen occurred at pH 5.5 and in 8 preparations was 380 +/- 237 ng kinin/h/10(6) mast cells (means +/- SD). Thus, human lung mast cells contain a kininogenase that is released during, and may participate in, IgE-mediated inflammatory disorders in humans.