The IgE receptor-dependent in vitro mediator release in basophils is characterized by a large interindividual variability both in normal and atopic subjects. The mechanism and the clinical impact of this finding, however, is largely unclear. The aim of the present study was to examine the role of surface-bound IgE and of response-modifying cytokines such as interleukin 3 (IL-3) as possible factors determining basophil releasability in atopic patients and normal controls. Cells from 30 individuals (6 with urticaria, 7 with asthma, 7 with atopic dermatitis, and 30 healthy controls) were isolated and stimulated for mediator release by IL-3 and different triggering antibodies directed against IgE or IgE receptor. Our data suggest that serum IgE levels and basophil receptor occupancy with IgE are not involved in the mechanism of basophil releasability. Furthermore, IL-3-induced similar effects on mediator release in almost all individuals, rather excluding the possibility that releasability is regulated by cytokine priming of basophils. Interestingly, we found that patients with atopic disease have a reduced capacity of releasing mediators upon activation, the mechanism of which is unclear. In conclusion, our findings support the hypothesis that basophil releasability is dependent on cell-immanent mechanisms in basophils, which may be altered in selected atopic patients.
Studies on the regulation of IgE synthesis by IgE cellular receptors or fragments thereof, the so-called IgE-binding factors, are currently attracting much attention. Even more important may be some lymphokines such as interleukin 4 and interferon gamma which have been shown to have opposite influences on IgE synthesis, both in vitro and in vivo. However, the role of anti-isotypic anti-IgE antibodies, which have been shown to occur frequently during an IgE response, also deserves to be further investigated. At the effector level, namely the development of immediate and late allergic reactions following renewed encounter with allergen, new concepts such as variable releasability and priming of effector cells by lymphokines have opened new investigative pathways. Indeed, pretreatment of neutrophils by granulocyte/monocyte colony-stimulating factor or basophils by interleukin 3 appears essential for production or optimal release of inflammatory mediators such as histamine, leukotrienes, or platelet-activating factor. Even the successive impact of purified lymphokines such as interleukins 3 and 8 on basophils may suffice to initiate mediator release. These phenomena may explain, at the molecular level, the induction of a state of hyperreactivity characteristic of the late-phase allergic reaction. They also suggest new immunopharmacological approaches for the treatment of allergy.
We have previously shown that schistosome-derived inhibitory factors (SDIF) inhibited lymphocyte proliferation and induced immunosuppression. Crude SDIF was purified by successive gel filtration and reverse-phase high-performance liquid chromatography. Purified SDIF preparations strongly inhibited the proliferation of different T cell line cells, while other cell lines (B cells, macrophages and fibroblasts) were almost not affected by SDIF. The inhibition of T cell proliferation by SDIF was not mediated through an Interleukin-2-dependent mechanism since both Interleukin-2-dependent and -independent T cells were inhibited. SDIF-activity was absorbed by cells in a time- and cell-number-dependent fashion at 4°C, suggesting the existence of a possible receptor for SDIF. However, the difference in sensitivity to SDIF proliferation inhibition could not be attributed to the presence or absence of this receptor since cells from SDIF-sensitive and SDIF-resistant cell lines absorbed SDIF activity in the same way.
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