Stimulus-dependent leukotriene release from human basophils: A comparative study of C5a and F-met-leuphe

Previous studies of human basophil mediator release have noted that the bacterial peptide fmet-Ieu-phe and the anaphylatoxin C5a induce comparable levels of histamine release while only fmet peptide Induces leukotriene release. Since 5-lipoxygenase metabolism of arachidonic acid is calcium dependent, we examined the characteristics of the human basophil [Cat response which follows its activation by either fmet peptide or C5a. While the peak [Ca response was essentially identical for these two stimuli, fmet peptide induced a prolonged increase in [Cat i while C5a stimulated only a transient increase in [Cat J that was essentially over within 2 minutes of adding the stimulus. Simultaneous addition of EDTA with fmet peptide revealed the two phases of the [Cat ] response and demonstrated that leukotriene release was dependent on an elevated (Ca level in the 2-5 minutes following challenge. Enhancement of Ieukotriene release induced by C5a by agents such as staurosporine and interleukin-3 also produced a [Ca kinetic curve which resembled fmet piptide. Single cell studies of the [Ca response could detect no subpopulations of cells which responded preferentially to fmet peptide or C5a, eliminating the possibility that the ability of fmet peptide to induce Ieukotrlene was a result of its action on a functionally distinct population of basophils. Key words: calcium, staurosporine, interleukin-