Bronchospasm induced in allergic patients by in vitro released mediators. II. Analysis of possible mechanisms

In a previous report, it was shown that cultures of peripheral blood leukocytes, from allergic individuals, in the presence of antigen will produce bronchospasm inducing agents in the supernatants. In this study, the responsibility of several mediators was analyzed, i.e., histamine, IgE, prostaglandins E2 and F2 alpha and leukotrienes C4. The results failed to demonstrate a significant release of histamine. Measurable amount of IgE could be recovered from active supernatants. Following removal of IgE and IgE-antigen complexes, the immediate bronchospastic response disappeared without so many changes in the delayed response. PGE2 and PGF2 alpha could be demonstrated in the active supernatants, which could be blocked by indomethacin. No significant differences in the bronchial challenge could be demonstrated between the two samples. Samples contained significant amount of leucotrienes C4. Treatment of cultures with NDGA (cyclooxygenase inhibitor) blocked almost completely the bronchial response. Therefore, in this assay, IgE, IgE-antigen complexes and leukotrienes C4 seem to play a major role in the induction of bronchospasm in sensitized individuals. We are clearly aware that the mediators production in vitro may eventually reflect only part of the events taking place in vivo. Nevertheless, this model allows the analysis of several major mediators and eventually some of their interactions. The role of PAF is now under study.