Release Of Preformed Mediators Research Articles

Possible role of phospholipase A 2 in triggering histamine secretion from human basophils in vitro

We have investigated the possibility that phospholipase A 2 (PLA 2) activation plays a role in immediate hypersensitivity reactions. Two agents, p-bromophenacyl bromide (BPB) and mepacrine, which inhibit PLA 2 activity in several tissues, cause a dose-dependent inhibition of histamine release from human basophils induced by several immunologic (i.e., antigen and anti-IgE) and nonimmunologic (i.e., formyl-methionine-containing peptide [(f-met peptide)] and the Ca 2+ ionophore, A23187) stimuli. The inhibitory effect of BPB on histamine release is irreversible and extremely rapid. BPB is inhibitory in the whole reaction as well as in the first and second stage of antigen- and anti-IgE-induced histamine release. Increasing the Ca 2+ concentrations in the extracellular medium partially blocks the inhibitory effect of BPB. BPB, however, is not a competitive antagonist of the effect of Ca 2+ suggesting that the two agents act on distinct enzymatic sites. The inhibitory effect of BPB in the presence of exogenous arachidonic acid (AA) was less marked than in the absence of AA. These data suggest that the activation of cell surface receptors and/or the intracellular translocation of Ca 2+ by the ionophore A23187 activates a basophil PLA 2 which plays an essential role in the control of the release of preformed mediators.

Formation of slow-reacting substance of anaphylaxis in human lung tissue and cells before release.

The capacity to extract slow-reacting substance of anaphylaxis (SRS-A) from human lung tissue or cells after immunologic activation, together with the measurement of SRS-A in both the extract and the surrounding fluid, permits study of total SRS-A generation. That the material extracted is SRS-A was established by both differential bioassay and purification. SRS-A accumulation was entirely intracellular after limited IgE-dependent direct or reversed anaphylactic activation. Intracellular accumulation also generally preceded release, with generation of SRS-A continuing well beyond a plateau in the cellular SRS-A level and the release of preformed mediators. The quantity of SRS-A generated after immunologic activation was modulated by the introduction of exogenous cyclic nucleotides, revealing a site of cyclic nucleotide action distinct from that on mediator release. The capacity to determine not only the release of preformed mediators but also the generation of a newly formed mediator, the sum of SRS-A in cells and supernate, adds an additional dimension to the analysis of the cellular events of immediate hypersensitivity.